التفاصيل البيبلوغرافية
| العنوان: |
Targeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal cancers. |
| المؤلفون: |
Yu Wang, Adachi, Yasushi, Imsumran, Arisa, Yamamoto, Hiroyuki, Wenhua Piao, Hua Li, Ii, Masanori, Arimura, Yoshiaki, Mi Park, Dalrae Kim, Choon-Taek Lee, Carbone, David, Imai, Kohzoh, Shinomura, Yasuhisa |
| المصدر: |
Journal of Gastroenterology; Feb2010, Vol. 45 Issue 2, p159-170, 12p, 6 Graphs |
| مصطلحات موضوعية: |
HYPOGLYCEMIC agents, DRUG therapy, CANCER education, INSULIN receptors, CELL culture, LIVER tumors, SQUAMOUS cell carcinoma |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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