Targeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal cancers View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-11-10

AUTHORS

Yu Wang, Yasushi Adachi, Arisa Imsumran, Hiroyuki Yamamoto, Wenhua Piao, Hua Li, Masanori Ii, Yoshiaki Arimura, Mi Young Park, Dalrae Kim, Choon-Taek Lee, David P. Carbone, Kohzoh Imai, Yasuhisa Shinomura

ABSTRACT

Background and aimsInsulin-like growth factor (IGF)-I receptor (IGF-IR) signaling plays important parts in both the tumorigenicity and progression of digestive/gastrointestinal malignancies. In this study, we sought to test the effectiveness of a practical approach to blocking IGF-IR signaling using RNA interference delivered by recombinant adenoviruses.MethodsWe constructed a recombinant adenovirus expressing short hairpin RNA targeting IGF-IR (shIGF-IR) and assessed its effect on signal transduction, proliferation, and survival in digestive/gastrointestinal cancer cell lines representing colorectal, gastric, and pancreatic adenocarcinoma, esophageal squamous cell carcinoma, and hepatoma. We analyzed the effects of shIGF-IR alone and with chemotherapy in vitro and in nude mouse xenografts, as well as on insulin signaling and hybrid receptor formation between IGF-IR and insulin receptor.ResultsshIGF-IR blocked expression and autophosphorylation of IGF-IR and downstream signaling by the IGFs, but not by insulin. shIGF-IR suppressed proliferation and carcinogenicity in vitro and up-regulated apoptosis in a dose-dependent fashion. shIGF-IR augmented the effects of chemotherapy on in vitro growth and apoptosis induction. Moreover, the combination of shIGF-IR and chemotherapy was highly effective against tumors in mice. shIGF-IR reduced hybrid receptor formation without effect on expression of insulin receptor.ConclusionsshIGF-IR may have therapeutic utility in human digestive/gastrointestinal cancers, both alone and in combination with chemotherapy. More... »

PAGES

159-170

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00535-009-0151-6

DOI

http://dx.doi.org/10.1007/s00535-009-0151-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023037865

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19902140


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35 schema:description Background and aimsInsulin-like growth factor (IGF)-I receptor (IGF-IR) signaling plays important parts in both the tumorigenicity and progression of digestive/gastrointestinal malignancies. In this study, we sought to test the effectiveness of a practical approach to blocking IGF-IR signaling using RNA interference delivered by recombinant adenoviruses.MethodsWe constructed a recombinant adenovirus expressing short hairpin RNA targeting IGF-IR (shIGF-IR) and assessed its effect on signal transduction, proliferation, and survival in digestive/gastrointestinal cancer cell lines representing colorectal, gastric, and pancreatic adenocarcinoma, esophageal squamous cell carcinoma, and hepatoma. We analyzed the effects of shIGF-IR alone and with chemotherapy in vitro and in nude mouse xenografts, as well as on insulin signaling and hybrid receptor formation between IGF-IR and insulin receptor.ResultsshIGF-IR blocked expression and autophosphorylation of IGF-IR and downstream signaling by the IGFs, but not by insulin. shIGF-IR suppressed proliferation and carcinogenicity in vitro and up-regulated apoptosis in a dose-dependent fashion. shIGF-IR augmented the effects of chemotherapy on in vitro growth and apoptosis induction. Moreover, the combination of shIGF-IR and chemotherapy was highly effective against tumors in mice. shIGF-IR reduced hybrid receptor formation without effect on expression of insulin receptor.ConclusionsshIGF-IR may have therapeutic utility in human digestive/gastrointestinal cancers, both alone and in combination with chemotherapy.
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42 IGF
43 IGF-IR
44 MethodsWe
45 RNA
46 RNA interference
47 adenocarcinoma
48 adenovirus
49 apoptosis
50 apoptosis induction
51 approach
52 autophosphorylation
53 background
54 cancer
55 cancer cell lines
56 carcinogenicity
57 carcinoma
58 cell carcinoma
59 cell lines
60 chemotherapy
61 combination
62 dose-dependent fashion
63 downstream
64 effect
65 effect of chemotherapy
66 effectiveness
67 esophageal squamous cell carcinoma
68 expression
69 factors
70 fashion
71 formation
72 gastric
73 gastrointestinal cancer
74 gastrointestinal cancer cell lines
75 gastrointestinal malignancies
76 growth
77 growth factor
78 hairpin RNA
79 hepatoma
80 hybrid receptor formation
81 important part
82 induction
83 insulin
84 insulin receptor
85 insulin-like growth
86 interference
87 lines
88 malignancy
89 mice
90 mouse xenografts
91 nude mouse xenografts
92 pancreatic adenocarcinoma
93 part
94 practical approach
95 progression
96 proliferation
97 receptor formation
98 receptors
99 recombinant adenovirus
100 short hairpin RNA
101 signal transduction
102 squamous cell carcinoma
103 study
104 survival
105 therapeutic utility
106 transduction
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