Effects On Bionomics Of Human Osteosarcoma Cells By Lentivirus-mediated Rnai Knockdown Of IGF-1R

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 and this high-expression of IGF-1R maybe effect on the growth, proliferation , invasion, radiotolerance. Using small interfering RNA (siRNA) to inhibit gene expression has become an effective technique in studying gene function and gene therapy, and lentivirus vector has been developed to be a full-blown research methods. To explore its possibility as a therapeutic target for the treatment of osteosarcoma, small hairpin RNA (shRNA) by lentivirus-mediated siRNA methods (lentivirus-mediated RNAi) was employed to downregulate endogenous IGF-1R expression to study the function of IGF-1R in tumorigenesis and radioresistance of osteosarcoma cells. By RT-PCR and Western blotting, we showed that the IGF-1R expression was persistently and markedly reduced by one shRNA that 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 G0/G1 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 targeting IGF-1R could induce potent antitumor activity and radiosensitizing activity in human osteosarcomas.