STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-05-11

AUTHORS

A Horiguchi, T Asano, K Kuroda, A Sato, J Asakuma, K Ito, M Hayakawa, M Sumitomo, T Asano

ABSTRACT

Background:Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes that mediate cell survival, proliferation, and angiogenesis and is aberrantly activated in various types of malignancies, including renal cell carcinoma (RCC). We examined whether it could be a novel therapeutic target for RCC by using the STAT3 inhibitor WP1066.Methods:The antitumour activities and related mechanisms of WP1066 were investigated in vitro on renal cancer cell lines and in vivo on murine xenografts.Results:In Caki-1 and 786-O renal cancer cells, 5 μM WP1066 prevented the phosphorylation of STAT3, and 2.5 μM WP1066 significantly (P<0.01) inhibited cell survival and proliferation. WP1066 suppressed the expression of Bcl-2, induced apoptosis, and inhibited the basal and hypoxia-induced expression of HIF1α and HIF2α, as well as vascular endothelial growth factor secretion into cell culture medium. Human umbilical vascular endothelial cells cocultured with media from WP1066-treated cells showed significantly reduced tubulogenesis (P<0.05). Systemic oral administration of WP1066 to mice for 19 days significantly inhibited the growth of Caki-1 xenograft tumours (P<0.05), and pathological analysis of xenografts of WP1066-treated mice showed decreased immunostaining of phosphorylated STAT3 and reduced length of CD34-positive vessels (P<0.05).Conclusion:Our results suggest that using WP1066 to inhibit the STAT3 signalling pathway could be a novel therapeutic strategy against RCC. More... »

PAGES

1592-1599

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6605691

DOI

http://dx.doi.org/10.1038/sj.bjc.6605691

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012090202

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20461084


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antineoplastic Agents", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Apoptosis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Basic Helix-Loop-Helix Transcription Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carcinoma, Renal Cell", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Proliferation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Survival", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cells, Cultured", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Expression Regulation, Neoplastic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hypoxia-Inducible Factor 1, alpha Subunit", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Kidney Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice, Nude", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Neovascularization, Pathologic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Pyridines", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "STAT3 Transcription Factor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Tyrphostins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Vascular Endothelial Growth Factor A", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Xenograft Model Antitumor Assays", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan", 
          "id": "http://www.grid.ac/institutes/grid.416614.0", 
          "name": [
            "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Horiguchi", 
        "givenName": "A", 
        "id": "sg:person.0616322445.22", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0616322445.22"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan", 
          "id": "http://www.grid.ac/institutes/grid.416614.0", 
          "name": [
            "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Asano", 
        "givenName": "T", 
        "id": "sg:person.01103061431.15", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01103061431.15"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan", 
          "id": "http://www.grid.ac/institutes/grid.416614.0", 
          "name": [
            "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kuroda", 
        "givenName": "K", 
        "id": "sg:person.01224662271.36", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01224662271.36"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan", 
          "id": "http://www.grid.ac/institutes/grid.416614.0", 
          "name": [
            "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sato", 
        "givenName": "A", 
        "id": "sg:person.0731733171.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0731733171.02"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan", 
          "id": "http://www.grid.ac/institutes/grid.416614.0", 
          "name": [
            "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Asakuma", 
        "givenName": "J", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan", 
          "id": "http://www.grid.ac/institutes/grid.416614.0", 
          "name": [
            "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ito", 
        "givenName": "K", 
        "id": "sg:person.0742101353.31", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0742101353.31"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan", 
          "id": "http://www.grid.ac/institutes/grid.416614.0", 
          "name": [
            "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hayakawa", 
        "givenName": "M", 
        "id": "sg:person.01056716414.39", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01056716414.39"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan", 
          "id": "http://www.grid.ac/institutes/grid.416614.0", 
          "name": [
            "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sumitomo", 
        "givenName": "M", 
        "id": "sg:person.01257012245.91", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257012245.91"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan", 
          "id": "http://www.grid.ac/institutes/grid.416614.0", 
          "name": [
            "Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Asano", 
        "givenName": "T", 
        "id": "sg:person.011653555242.33", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011653555242.33"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/cr.2008.18", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008695398", 
          "https://doi.org/10.1038/cr.2008.18"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/379645a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027170927", 
          "https://doi.org/10.1038/379645a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1206122", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041380684", 
          "https://doi.org/10.1038/sj.onc.1206122"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1207703", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046741130", 
          "https://doi.org/10.1038/sj.onc.1207703"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1208719", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044728544", 
          "https://doi.org/10.1038/sj.onc.1208719"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bjc.6605167", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013222336", 
          "https://doi.org/10.1038/sj.bjc.6605167"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1205260", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006935562", 
          "https://doi.org/10.1038/sj.onc.1205260"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bjc.6605437", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016108440", 
          "https://doi.org/10.1038/sj.bjc.6605437"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1210031", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031711164", 
          "https://doi.org/10.1038/sj.onc.1210031"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2010-05-11", 
    "datePublishedReg": "2010-05-11", 
    "description": "Background:Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes that mediate cell survival, proliferation, and angiogenesis and is aberrantly activated in various types of malignancies, including renal cell carcinoma (RCC). We examined whether it could be a novel therapeutic target for RCC by using the STAT3 inhibitor WP1066.Methods:The antitumour activities and related mechanisms of WP1066 were investigated in vitro on renal cancer cell lines and in vivo on murine xenografts.Results:In Caki-1 and 786-O renal cancer cells, 5\u2009\u03bcM WP1066 prevented the phosphorylation of STAT3, and 2.5\u2009\u03bcM WP1066 significantly (P<0.01) inhibited cell survival and proliferation. WP1066 suppressed the expression of Bcl-2, induced apoptosis, and inhibited the basal and hypoxia-induced expression of HIF1\u03b1 and HIF2\u03b1, as well as vascular endothelial growth factor secretion into cell culture medium. Human umbilical vascular endothelial cells cocultured with media from WP1066-treated cells showed significantly reduced tubulogenesis (P<0.05). Systemic oral administration of WP1066 to mice for 19 days significantly inhibited the growth of Caki-1 xenograft tumours (P<0.05), and pathological analysis of xenografts of WP1066-treated mice showed decreased immunostaining of phosphorylated STAT3 and reduced length of CD34-positive vessels (P<0.05).Conclusion:Our results suggest that using WP1066 to inhibit the STAT3 signalling pathway could be a novel therapeutic strategy against RCC.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/sj.bjc.6605691", 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1017082", 
        "issn": [
          "0007-0920", 
          "1532-1827"
        ], 
        "name": "British Journal of Cancer", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "11", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "102"
      }
    ], 
    "keywords": [
      "renal cell carcinoma", 
      "cell survival", 
      "cell carcinoma", 
      "expression of genes", 
      "renal cancer cells", 
      "phosphorylation of STAT3", 
      "human umbilical vascular endothelial cells", 
      "systemic oral administration", 
      "hypoxia-induced expression", 
      "types of malignancies", 
      "vascular endothelial growth factor (VEGF) secretion", 
      "renal cancer cell lines", 
      "novel therapeutic target", 
      "CD34-positive vessels", 
      "novel therapeutic strategies", 
      "signal transducer", 
      "novel therapeutic agents", 
      "transcription 3", 
      "growth factor secretion", 
      "vascular endothelial cells", 
      "STAT3 inhibitor", 
      "phosphorylated STAT3", 
      "cancer cell lines", 
      "WP1066", 
      "oral administration", 
      "xenograft tumors", 
      "pathological analysis", 
      "Bcl-2", 
      "therapeutic strategies", 
      "therapeutic target", 
      "murine xenografts", 
      "cell lines", 
      "cancer cells", 
      "STAT3", 
      "Caki-1", 
      "factor secretion", 
      "antitumour activity", 
      "therapeutic agents", 
      "endothelial cells", 
      "expression", 
      "cell culture medium", 
      "carcinoma", 
      "xenografts", 
      "cells", 
      "culture medium", 
      "mice", 
      "proliferation", 
      "survival", 
      "related mechanisms", 
      "genes", 
      "phosphorylation", 
      "tubulogenesis", 
      "HIF2\u03b1", 
      "apoptosis", 
      "HIF1\u03b1", 
      "activator", 
      "malignancy", 
      "pathway", 
      "tumors", 
      "administration", 
      "secretion", 
      "angiogenesis", 
      "basal", 
      "vivo", 
      "inhibitors", 
      "days", 
      "vessels", 
      "growth", 
      "target", 
      "agents", 
      "mechanism", 
      "lines", 
      "activity", 
      "\u03bcM", 
      "medium", 
      "transducer", 
      "strategies", 
      "length", 
      "analysis", 
      "types", 
      "results"
    ], 
    "name": "STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma", 
    "pagination": "1592-1599", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1012090202"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/sj.bjc.6605691"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "20461084"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/sj.bjc.6605691", 
      "https://app.dimensions.ai/details/publication/pub.1012090202"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-08-04T16:59", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220804/entities/gbq_results/article/article_506.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/sj.bjc.6605691"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/sj.bjc.6605691'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/sj.bjc.6605691'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.bjc.6605691'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.bjc.6605691'


 

This table displays all metadata directly associated to this object as RDF triples.

313 TRIPLES      21 PREDICATES      135 URIs      118 LITERALS      27 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/sj.bjc.6605691 schema:about N08238eef67424f62b05a06583e9e3f52
2 N0e61b62f159b466d8b30f1ff47080ec0
3 N1a9cd415e2584dc0ae92abed08bff8d6
4 N3adf3593e5564a16a6d51bbfa457346a
5 N53cd05d795b74355b3a9637a7d5c761d
6 N5681d9d3f18e4a1cbb1bf485cede0c8d
7 N64f02e10f01140ec836c17eec3a6aeaf
8 N67e94d4c2b5f46059edb1608aff0f144
9 N7bb8ea04702142c49a931269c3ec7eba
10 N7c8ba1059a9c46b6990da3f191411b5d
11 N8a00a56f214c405b9ce115cf42039c00
12 N8c32924579844f669197d2b9f86dfd81
13 N993ecf58a8c14f2fb350ccd4c1a4d4a1
14 N9a2c4b49a47c46ec9aad6bcc701a1310
15 Na3c6ccc18111454a80e1e81bb7aaa9c5
16 Nc4d71b148f8d4ae99649fee5f64cbd3e
17 Nc784cb36d5164820b7746ee3f5548d72
18 Nd14c48b10fd04bfdbc2e2274c41656a4
19 Nd902acc0985246c4b7bb7cee45069d79
20 Nf871bca313cc4615bef49fa9e05d2459
21 anzsrc-for:11
22 anzsrc-for:1112
23 schema:author N604d40a49ad940a5b9b5bd3a37e3acb8
24 schema:citation sg:pub.10.1038/379645a0
25 sg:pub.10.1038/cr.2008.18
26 sg:pub.10.1038/sj.bjc.6605167
27 sg:pub.10.1038/sj.bjc.6605437
28 sg:pub.10.1038/sj.onc.1205260
29 sg:pub.10.1038/sj.onc.1206122
30 sg:pub.10.1038/sj.onc.1207703
31 sg:pub.10.1038/sj.onc.1208719
32 sg:pub.10.1038/sj.onc.1210031
33 schema:datePublished 2010-05-11
34 schema:datePublishedReg 2010-05-11
35 schema:description Background:Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes that mediate cell survival, proliferation, and angiogenesis and is aberrantly activated in various types of malignancies, including renal cell carcinoma (RCC). We examined whether it could be a novel therapeutic target for RCC by using the STAT3 inhibitor WP1066.Methods:The antitumour activities and related mechanisms of WP1066 were investigated in vitro on renal cancer cell lines and in vivo on murine xenografts.Results:In Caki-1 and 786-O renal cancer cells, 5 μM WP1066 prevented the phosphorylation of STAT3, and 2.5 μM WP1066 significantly (P<0.01) inhibited cell survival and proliferation. WP1066 suppressed the expression of Bcl-2, induced apoptosis, and inhibited the basal and hypoxia-induced expression of HIF1α and HIF2α, as well as vascular endothelial growth factor secretion into cell culture medium. Human umbilical vascular endothelial cells cocultured with media from WP1066-treated cells showed significantly reduced tubulogenesis (P<0.05). Systemic oral administration of WP1066 to mice for 19 days significantly inhibited the growth of Caki-1 xenograft tumours (P<0.05), and pathological analysis of xenografts of WP1066-treated mice showed decreased immunostaining of phosphorylated STAT3 and reduced length of CD34-positive vessels (P<0.05).Conclusion:Our results suggest that using WP1066 to inhibit the STAT3 signalling pathway could be a novel therapeutic strategy against RCC.
36 schema:genre article
37 schema:isAccessibleForFree true
38 schema:isPartOf N39c27b55fe7e4984ab31a752716603b2
39 Ne681aa835f3740588715d8a35f2e1083
40 sg:journal.1017082
41 schema:keywords Bcl-2
42 CD34-positive vessels
43 Caki-1
44 HIF1α
45 HIF2α
46 STAT3
47 STAT3 inhibitor
48 WP1066
49 activator
50 activity
51 administration
52 agents
53 analysis
54 angiogenesis
55 antitumour activity
56 apoptosis
57 basal
58 cancer cell lines
59 cancer cells
60 carcinoma
61 cell carcinoma
62 cell culture medium
63 cell lines
64 cell survival
65 cells
66 culture medium
67 days
68 endothelial cells
69 expression
70 expression of genes
71 factor secretion
72 genes
73 growth
74 growth factor secretion
75 human umbilical vascular endothelial cells
76 hypoxia-induced expression
77 inhibitors
78 length
79 lines
80 malignancy
81 mechanism
82 medium
83 mice
84 murine xenografts
85 novel therapeutic agents
86 novel therapeutic strategies
87 novel therapeutic target
88 oral administration
89 pathological analysis
90 pathway
91 phosphorylated STAT3
92 phosphorylation
93 phosphorylation of STAT3
94 proliferation
95 related mechanisms
96 renal cancer cell lines
97 renal cancer cells
98 renal cell carcinoma
99 results
100 secretion
101 signal transducer
102 strategies
103 survival
104 systemic oral administration
105 target
106 therapeutic agents
107 therapeutic strategies
108 therapeutic target
109 transcription 3
110 transducer
111 tubulogenesis
112 tumors
113 types
114 types of malignancies
115 vascular endothelial cells
116 vascular endothelial growth factor (VEGF) secretion
117 vessels
118 vivo
119 xenograft tumors
120 xenografts
121 μM
122 schema:name STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma
123 schema:pagination 1592-1599
124 schema:productId N5d4e244a3341402c9eea9f7e2c1a66cc
125 N9f1e3f4d1dda48f0a57c055f5b684b14
126 Nd948c8585c5f489c842afc13b94497af
127 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012090202
128 https://doi.org/10.1038/sj.bjc.6605691
129 schema:sdDatePublished 2022-08-04T16:59
130 schema:sdLicense https://scigraph.springernature.com/explorer/license/
131 schema:sdPublisher Nd542f3d467dd4857a6a700e939cc1b6a
132 schema:url https://doi.org/10.1038/sj.bjc.6605691
133 sgo:license sg:explorer/license/
134 sgo:sdDataset articles
135 rdf:type schema:ScholarlyArticle
136 N08238eef67424f62b05a06583e9e3f52 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
137 schema:name Animals
138 rdf:type schema:DefinedTerm
139 N0e61b62f159b466d8b30f1ff47080ec0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
140 schema:name Cell Proliferation
141 rdf:type schema:DefinedTerm
142 N1a9cd415e2584dc0ae92abed08bff8d6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
143 schema:name Xenograft Model Antitumor Assays
144 rdf:type schema:DefinedTerm
145 N21a49205e0c04e8b923a04212b5fb009 schema:affiliation grid-institutes:grid.416614.0
146 schema:familyName Asakuma
147 schema:givenName J
148 rdf:type schema:Person
149 N39c27b55fe7e4984ab31a752716603b2 schema:volumeNumber 102
150 rdf:type schema:PublicationVolume
151 N3adf3593e5564a16a6d51bbfa457346a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
152 schema:name Tyrphostins
153 rdf:type schema:DefinedTerm
154 N4ca70b8e905348248e5ab97c9d7e4a0b rdf:first sg:person.01056716414.39
155 rdf:rest N4e03f2420756443fb243423c21310e1f
156 N4e03f2420756443fb243423c21310e1f rdf:first sg:person.01257012245.91
157 rdf:rest Nfb58ee14712b4d7697c4babd60039606
158 N513350f28aaf457ca674a8b9f1e9b113 rdf:first N21a49205e0c04e8b923a04212b5fb009
159 rdf:rest N73b93d85141040feb4c42ae1f5668846
160 N53cd05d795b74355b3a9637a7d5c761d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name Gene Expression Regulation, Neoplastic
162 rdf:type schema:DefinedTerm
163 N5681d9d3f18e4a1cbb1bf485cede0c8d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
164 schema:name Kidney Neoplasms
165 rdf:type schema:DefinedTerm
166 N5d4e244a3341402c9eea9f7e2c1a66cc schema:name dimensions_id
167 schema:value pub.1012090202
168 rdf:type schema:PropertyValue
169 N604d40a49ad940a5b9b5bd3a37e3acb8 rdf:first sg:person.0616322445.22
170 rdf:rest N78f8d0bf518940ce90f382a8861cf3cd
171 N64f02e10f01140ec836c17eec3a6aeaf schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
172 schema:name Mice, Nude
173 rdf:type schema:DefinedTerm
174 N6613ea97ac2e4875a5c5b31e247b68db rdf:first sg:person.01224662271.36
175 rdf:rest Ne657d8d9022a4dd4b6cb7547662edd39
176 N67e94d4c2b5f46059edb1608aff0f144 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
177 schema:name Cell Survival
178 rdf:type schema:DefinedTerm
179 N73b93d85141040feb4c42ae1f5668846 rdf:first sg:person.0742101353.31
180 rdf:rest N4ca70b8e905348248e5ab97c9d7e4a0b
181 N78f8d0bf518940ce90f382a8861cf3cd rdf:first sg:person.01103061431.15
182 rdf:rest N6613ea97ac2e4875a5c5b31e247b68db
183 N7bb8ea04702142c49a931269c3ec7eba schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
184 schema:name Antineoplastic Agents
185 rdf:type schema:DefinedTerm
186 N7c8ba1059a9c46b6990da3f191411b5d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
187 schema:name Carcinoma, Renal Cell
188 rdf:type schema:DefinedTerm
189 N8a00a56f214c405b9ce115cf42039c00 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
190 schema:name STAT3 Transcription Factor
191 rdf:type schema:DefinedTerm
192 N8c32924579844f669197d2b9f86dfd81 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
193 schema:name Neovascularization, Pathologic
194 rdf:type schema:DefinedTerm
195 N993ecf58a8c14f2fb350ccd4c1a4d4a1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
196 schema:name Mice
197 rdf:type schema:DefinedTerm
198 N9a2c4b49a47c46ec9aad6bcc701a1310 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
199 schema:name Hypoxia-Inducible Factor 1, alpha Subunit
200 rdf:type schema:DefinedTerm
201 N9f1e3f4d1dda48f0a57c055f5b684b14 schema:name doi
202 schema:value 10.1038/sj.bjc.6605691
203 rdf:type schema:PropertyValue
204 Na3c6ccc18111454a80e1e81bb7aaa9c5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
205 schema:name Basic Helix-Loop-Helix Transcription Factors
206 rdf:type schema:DefinedTerm
207 Nc4d71b148f8d4ae99649fee5f64cbd3e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
208 schema:name Apoptosis
209 rdf:type schema:DefinedTerm
210 Nc784cb36d5164820b7746ee3f5548d72 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
211 schema:name Vascular Endothelial Growth Factor A
212 rdf:type schema:DefinedTerm
213 Nd14c48b10fd04bfdbc2e2274c41656a4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
214 schema:name Pyridines
215 rdf:type schema:DefinedTerm
216 Nd542f3d467dd4857a6a700e939cc1b6a schema:name Springer Nature - SN SciGraph project
217 rdf:type schema:Organization
218 Nd902acc0985246c4b7bb7cee45069d79 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
219 schema:name Humans
220 rdf:type schema:DefinedTerm
221 Nd948c8585c5f489c842afc13b94497af schema:name pubmed_id
222 schema:value 20461084
223 rdf:type schema:PropertyValue
224 Ne657d8d9022a4dd4b6cb7547662edd39 rdf:first sg:person.0731733171.02
225 rdf:rest N513350f28aaf457ca674a8b9f1e9b113
226 Ne681aa835f3740588715d8a35f2e1083 schema:issueNumber 11
227 rdf:type schema:PublicationIssue
228 Nf871bca313cc4615bef49fa9e05d2459 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
229 schema:name Cells, Cultured
230 rdf:type schema:DefinedTerm
231 Nfb58ee14712b4d7697c4babd60039606 rdf:first sg:person.011653555242.33
232 rdf:rest rdf:nil
233 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
234 schema:name Medical and Health Sciences
235 rdf:type schema:DefinedTerm
236 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
237 schema:name Oncology and Carcinogenesis
238 rdf:type schema:DefinedTerm
239 sg:journal.1017082 schema:issn 0007-0920
240 1532-1827
241 schema:name British Journal of Cancer
242 schema:publisher Springer Nature
243 rdf:type schema:Periodical
244 sg:person.01056716414.39 schema:affiliation grid-institutes:grid.416614.0
245 schema:familyName Hayakawa
246 schema:givenName M
247 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01056716414.39
248 rdf:type schema:Person
249 sg:person.01103061431.15 schema:affiliation grid-institutes:grid.416614.0
250 schema:familyName Asano
251 schema:givenName T
252 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01103061431.15
253 rdf:type schema:Person
254 sg:person.011653555242.33 schema:affiliation grid-institutes:grid.416614.0
255 schema:familyName Asano
256 schema:givenName T
257 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011653555242.33
258 rdf:type schema:Person
259 sg:person.01224662271.36 schema:affiliation grid-institutes:grid.416614.0
260 schema:familyName Kuroda
261 schema:givenName K
262 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01224662271.36
263 rdf:type schema:Person
264 sg:person.01257012245.91 schema:affiliation grid-institutes:grid.416614.0
265 schema:familyName Sumitomo
266 schema:givenName M
267 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257012245.91
268 rdf:type schema:Person
269 sg:person.0616322445.22 schema:affiliation grid-institutes:grid.416614.0
270 schema:familyName Horiguchi
271 schema:givenName A
272 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0616322445.22
273 rdf:type schema:Person
274 sg:person.0731733171.02 schema:affiliation grid-institutes:grid.416614.0
275 schema:familyName Sato
276 schema:givenName A
277 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0731733171.02
278 rdf:type schema:Person
279 sg:person.0742101353.31 schema:affiliation grid-institutes:grid.416614.0
280 schema:familyName Ito
281 schema:givenName K
282 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0742101353.31
283 rdf:type schema:Person
284 sg:pub.10.1038/379645a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027170927
285 https://doi.org/10.1038/379645a0
286 rdf:type schema:CreativeWork
287 sg:pub.10.1038/cr.2008.18 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008695398
288 https://doi.org/10.1038/cr.2008.18
289 rdf:type schema:CreativeWork
290 sg:pub.10.1038/sj.bjc.6605167 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013222336
291 https://doi.org/10.1038/sj.bjc.6605167
292 rdf:type schema:CreativeWork
293 sg:pub.10.1038/sj.bjc.6605437 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016108440
294 https://doi.org/10.1038/sj.bjc.6605437
295 rdf:type schema:CreativeWork
296 sg:pub.10.1038/sj.onc.1205260 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006935562
297 https://doi.org/10.1038/sj.onc.1205260
298 rdf:type schema:CreativeWork
299 sg:pub.10.1038/sj.onc.1206122 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041380684
300 https://doi.org/10.1038/sj.onc.1206122
301 rdf:type schema:CreativeWork
302 sg:pub.10.1038/sj.onc.1207703 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046741130
303 https://doi.org/10.1038/sj.onc.1207703
304 rdf:type schema:CreativeWork
305 sg:pub.10.1038/sj.onc.1208719 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044728544
306 https://doi.org/10.1038/sj.onc.1208719
307 rdf:type schema:CreativeWork
308 sg:pub.10.1038/sj.onc.1210031 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031711164
309 https://doi.org/10.1038/sj.onc.1210031
310 rdf:type schema:CreativeWork
311 grid-institutes:grid.416614.0 schema:alternateName Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan
312 schema:name Department of Urology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa-City, Saitama, Japan
313 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...