Effects of geldanamycin on cell proliferation and apoptosis of human ovarian cancer cell line SKOV3 and their mechanism / 肿瘤

ABSTRACT

Objective: To investigate the cytotoxic effects of geldanamycin on human ovarian cancer SKOV3 cells, and to explore the possible mechanisms of apoptosis and cell proliferation inhibition of SKOV3 cells induced by geldanamycin. Methods: MTT method was performed to evaluate the inhibitory effects of geldanamycin alone or in combination with cisplatin on proliferation of SKOV3 cells. Cell cycle and apoptosis rate of SKOV3 cells treated with geldanamycin were detected by flow cytometry. The expressions of Akt and Raf-1 proteins were examined by immunocytochemistry and flow cytometry. Results: The proliferation of SKOV3 cells was inhibited by different concentrations of geldanamycin in a time- and dose-dependent manners (P<0.05). Different concentrations of geldanamycin strengthened the inhibitory effect of cisplatin on proliferation of SKOV3 cells, and this inhibitory effect was strengthened with the increased concentration of geldanamycin within a certain concentration range. The apoptosis rate of SKOV3 cells was raised up gradually after treatment with 0-2000 nmol/L geldanamycin for 48 h, and the number of cells in G2/M phase was increased significantly (P<0.05). The results of immunocytochemistry and flow cytometry showed that the expressions of Akt and Raf-1 proteins in SKOV3 cells induced by geldanamycin were significantly down-regulated in a dose-dependent manner (P<0.05). Conclusion: Geldanamycin can inhibit the cell proliferation and induce the apoptosis of human ovarian cancer SKOV3 cells in vitro , which may be associated with downregulation of the expressions of Akt and Raf-1 proteins. Copyright© 2011 by TUMOR.