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01.02.2010 | Original Article—Alimentary Tract

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

verfasst von: 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

Erschienen in: Journal of Gastroenterology | Ausgabe 2/2010

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Abstract

Background and aims

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.

Methods

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.

Results

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.

Conclusions

shIGF-IR may have therapeutic utility in human digestive/gastrointestinal cancers, both alone and in combination with chemotherapy.

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Titel: Targeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal cancers
verfasst von: 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
Publikationsdatum: 01.02.2010
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 2/2010
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-009-0151-6

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