title: Lentivirus-mediated shRNA targeting insulin-like growth factor-1 receptor (IGF-1R) enhances chemosensitivity of osteosarcoma cells in vitro and in vivo.
abstract: The overexpression of the type 1 insulin-like growth factor receptor (IGF-1R) has been reported to be associated with malignant transformation, tumor development and chemo- or radioresistance of tumor cells. Previously, we have reported that inhibition of IGF-1R could reverse the radioresistance of human osteosarcoma cells. However, whether inhibition of IGF-1R could enhance chemosensitivity of ostesosarcoma cells is unclear. In this study, lentivirus-mediated shRNA was employed to downregulate endogenous IGF-1R expression to study the function of IGF-1R in chemoresistance of osteosarcoma cells. Results showed that lentivirus-mediated shRNA targeting IGF-1R combined with chemotherapy (CDDP or DTX) could lead to growth suppression of osteosarcoma cells not only in vitro but also in vivo. Moreover, inhibition of IGF-1R gene combined with chemotherapy also synergistically enhanced Caspase-3-mediated apoptosis of osteosarcoma cells. The synergistical enhancement of apoptosis might be associated with downregulation of Bcl-2 and upregulation of Bax in osteosarcoma cells induced by IGF-1R inhibition. Therefore, the overexpression of IGF-1R gene might play important roles in chemoresistance of osteosarcoma cells, and lentivirus-mediated RNAi targeting IGF-1R would be an attractive anti-cancer strategy to chemosensitization of osteosarcoma cell.
authors.affiliation: Department of Orthopaedic Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, No 321 Zhongshan Road, Nanjing 210008, People's Republic of China.
authors.forename: Yin-He
authors.initials: YH
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Xiong
authors.forename: Shou-Feng
authors.initials: SF
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Chen
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Shi
authors.forename: Yong
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1