Rhein sensitizes human pancreatic cancer cells to EGFR inhibitors by inhibiting STAT3 pathway View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Lehe Yang, Shichong Lin, Yanting Kang, Youqun Xiang, Lingyuan Xu, Jifa Li, Xuanxuan Dai, Guang Liang, Xiaoying Huang, Chengguang Zhao

ABSTRACT

BACKGROUND: Rhein is a lipophilic anthraquinone extensively found in medicinal herbs. Emerging evidence suggests that rhein has significant antitumor effects, supporting its potential use as an antitumor agent. The IL6/STAT3 signaling pathway has been suggested as an attractive target for the discovery of novel cancer therapeutics. METHODS: The human pancreatic cancer cell lines AsPC-1, Patu8988T, BxPC-3 and PANC-1, and immunodeficient mice were chosen as models to study the effects of rhein. The potent antiproliferative and proapoptotic effects of rhein were examined by cell viability, cellular morphology, apoptosis and colony formation assays. The STAT3 luciferase report assay, immunostaining analysis and Western blot analysis revealed the inhibition of the IL6/STAT3 signaling axis. RESULTS: Apoptosis was induced by adjunctive use of rhein with epidermal growth factor receptor (EGFR) inhibitors in pancreatic cancer cells as verified by cell apoptosis analysis and changes in the expression level of apoptotic/anti-apoptotic proteins BCL-2, BAX, Caspase 3 and Cl-PARP. Suppression of the phosphorylation of STAT3 and EGFR were also observed as a result of the treatment with a combination of rhein and EGFR inhibitors. Most interestingly, it was found that rhein considerably sensitized cells to erlotinib, thus suppressing tumor growth in PANC-1 and BxPC-3 xenograft models. The in vivo anti-tumor effect was associated with increased apoptosis and combined inhibition of the STAT3 and EGFR pathways in tumor remnants. CONCLUSIONS: Rhein sensitizes human pancreatic cancer cells to EGFR inhibitors through inhibition of STAT3. Taken together, the results indicate that rhein offers a novel blueprint for pancreatic cancer therapy, particularly when combined with EGFR inhibitors. More... »

PAGES

31

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13046-018-1015-9

DOI

http://dx.doi.org/10.1186/s13046-018-1015-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111593732

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30674340


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    "description": "BACKGROUND: Rhein is a lipophilic anthraquinone extensively found in medicinal herbs. Emerging evidence suggests that rhein has significant antitumor effects, supporting its potential use as an antitumor agent. The IL6/STAT3 signaling pathway has been suggested as an attractive target for the discovery of novel cancer therapeutics.\nMETHODS: The human pancreatic cancer cell lines AsPC-1, Patu8988T, BxPC-3 and PANC-1, and immunodeficient mice were chosen as models to study the effects of rhein. The potent antiproliferative and proapoptotic effects of rhein were examined by cell viability, cellular morphology, apoptosis and colony formation assays. The STAT3 luciferase report assay, immunostaining analysis and Western blot analysis revealed the inhibition of the IL6/STAT3 signaling axis.\nRESULTS: Apoptosis was induced by adjunctive use of rhein with epidermal growth factor receptor (EGFR) inhibitors in pancreatic cancer cells as verified by cell apoptosis analysis and changes in the expression level of apoptotic/anti-apoptotic proteins BCL-2, BAX, Caspase 3 and Cl-PARP. Suppression of the phosphorylation of STAT3 and EGFR were also observed as a result of the treatment with a combination of rhein and EGFR inhibitors. Most interestingly, it was found that rhein considerably sensitized cells to erlotinib, thus suppressing tumor growth in PANC-1 and BxPC-3 xenograft models. The in vivo anti-tumor effect was associated with increased apoptosis and combined inhibition of the STAT3 and EGFR pathways in tumor remnants.\nCONCLUSIONS: Rhein sensitizes human pancreatic cancer cells to EGFR inhibitors through inhibition of STAT3. Taken together, the results indicate that rhein offers a novel blueprint for pancreatic cancer therapy, particularly when combined with EGFR inhibitors.", 
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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.10.1186/s13046-018-1015-9'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s13046-018-1015-9'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s13046-018-1015-9'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s13046-018-1015-9'


 

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