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

Cited 20 time in Web of Science Cited 20 time in Scopus
Authors
Wang, Yu; Adachi, Yasushi; Imsumran, Arisa; Yamamoto, Hiroyuki; Li, Hua; Arimura, Yoshiaki; Kim, Dalrae; Carbone, David P.; Shinomura, Yasuhisa; Imai, Kohzoh; Lee, Choon-Taek; Park, Mi Young; Ii, Masanori; Piao, Wenhua
Issue Date
2010-02
Publisher
SPRINGER TOKYO
Citation
JOURNAL OF GASTROENTEROLOGY; Vol.45 2; 159-170
Keywords
Combination therapyRNAiShort hairpin RNAInsulin like growth factor-I receptor (IGF-IR)Digestive/gastrointestinal cancers
Abstract
Insulin-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. We 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. shIGF-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. shIGF-IR may have therapeutic utility in human digestive/gastrointestinal cancers, both alone and in combination with chemotherapy.
ISSN
0944-1174
Language
English
URI
https://hdl.handle.net/10371/76574
DOI
https://doi.org/10.1007/s00535-009-0151-6
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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