Ontology type: schema:ScholarlyArticle
2009-11-10
AUTHORSYu 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
ABSTRACTBackground 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... »
PAGES159-170
http://scigraph.springernature.com/pub.10.1007/s00535-009-0151-6
DOIhttp://dx.doi.org/10.1007/s00535-009-0151-6
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/19902140
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