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.
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We are very grateful for the sincere help and technical support by department of biochemistry in Nanjing Medicine University.
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Wang, YH., Xiong, J., Wang, SF. et al. Lentivirus-mediated shRNA targeting insulin-like growth factor-1 receptor (IGF-1R) enhances chemosensitivity of osteosarcoma cells in vitro and in vivo. Mol Cell Biochem 341, 225–233 (2010). https://doi.org/10.1007/s11010-010-0453-2
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DOI: https://doi.org/10.1007/s11010-010-0453-2