Inhibitory effects of manumycin combined with cisplatin on the proliferation of human ovarian cancer cell line 3AO in vitro and in vivo / 肿瘤

ABSTRACT

Objective: To investigate the inhibition effects of manumycin combined with cisplatin (DDP) on the proliferation of human ovarian cancer cell line 3AO and the growth of transplantation tumors in nude mice, and to analyze its possible mechanisms. Methods: MTT colorimetric assay was performed to evaluate the cytotoxic effect of manumycin combined with DDP on 3AO cells. The model of nude mice bearing ovarian transplantation tumor was established. The expressions of survivin, NF-κB, vascular endothelial growth factor (VEGF) and caspase-3 proteins were detected by immunohistochemical method. The cell cycle distribution and apoptosis rate were examined by flow cytometry. Results: The proliferation of 3AO cells was inhibited by manumycin in a time- and dose-dependent manner (P <0.05). The manumycin of 10, 20, 40 or 60 μmol/L could strengthen the cytotoxic effect of DDP on 3AO cells. The tumor size in nude mice of each drug-treated group was significantly smaller than that of the control (untreated) group (P <0.05). Compared with the DDP alone and the manumycin alone group, the expressions of survivin, NF-κB and VEGF proteins were significantly down-regulated while the expression of caspase-3 protein was significantly up-regulated (P <0.05) in the combination (manumycin plus DDP) group (P <0.05). The apoptosis rates were increased gradually in the control group, manumycin group, DDP group and the combination group. In each drug-treated group, the number of cells in G0/ G 1 phase was decreased significantly, while which in G2/M phase was increased significantly (P <0.05), as compared with the control group. The number of cells in S phase did not show any changes in each group. Conclusion: The combination of manumycin and DDP shows an enhanced ability to inhibit the proliferation of human ovarian cancer cells 3AO and increase their apoptosis. This effect may be associated with the down-regulation of survivin, NF-VEGF expressions and the up-regulation of caspase-3 expression. Copyright© 2011 by the Editorial Board of Tumor.