title: Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits growth, reduces invasion, and enhances radiosensitivity in human osteosarcoma cells.
abstract: The type 1 insulin-like growth factor receptor (IGF-1R) is essential for tumorigenicity, tumor proliferation, and protection from apoptosis. IGF-1R overexpression has been found in many human cancers including osteosarcoma. To explore its possibility as a therapeutic target for the treatment of osteosarcoma, lentivirus-mediated siRNA was employed to downregulate endogenous IGF-1R expression to study the function of IGF-1R in tumorigenesis and radioresistance of osteosarcoma cells. The IGF-1R expression was persistently and markedly reduced by lentivirus-mediated RNAi. Downregulation of IGF-1R expression in osteosarcoma cells significantly suppressed their growth rates in vitro and reduced the potential of tumorigenicity in vivo. Moreover, the specific downregulation arrested cells in G(0)/G(1) phase of cell cycle and also induced apoptosis which correlated with the activation of Caspase-3. Furthermore, we also observed that suppression of IGF-1R could reduce the invasiveness of osteosarcoma cells and enhance their radiosensitivity. Our study suggested that lentivirus-mediated RNAi silencing targeting IGF-1R could induce potent antitumor activity and radiosensitizing activity in human osteosarcomas.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Hanzhong Road 140, 210029 Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Yin-He
authors.initials: YH
authors.lastname: Wang
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Qiu
authors.forename: Jin
authors.initials: J
authors.lastname: Xiong
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Chen
authors.forename: Deng-Shun
authors.initials: DS
authors.lastname: Miao
authors.forename: Wei
authors.initials: W
authors.lastname: De
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020868:Gene Silencing; D006801:Humans; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D017526:Receptor, IGF Type 1; D053148:Caspase 3