Underlying mechanism of 2-methoxyestradiol-induced apoptosis and growth arrest in SKOV3 human ovarian cancer cells.

OBJECTIVE: In this study, we sought to investigate the effects of 2-methoxyestradiol (2-ME) on cisplatin-induced apoptosis and growth inhibition in SKOV3 ovarian cancer cells.
MATERIALS AND METHODS: Cells were treated with 2-ME, carboplatin, or both, the control group, and cell viability and growth inhibition assays were performed using the MTT method. Apoptosis was detected by flow cytometry analysis. Reverse transcription polymerase chain reaction and western blotting were used to monitor the mRNA and protein expression of the pro-apoptotic genes bax and caspase-3 and the anti-apoptotic gene bcl-2. The phosphorylation of Bcl-2 protein was monitored by western blotting.
RESULTS: Cell viability was inhibited by all three treatments in a time-dependent manner. Importantly, the combination treatment resulted in significantly reduced cell growth compared with the other groups. The mRNA and protein expression of Bax and caspase-3 were increased in the combination treatment group, and the expression of Bcl-2 was decreased in the combination treatment group as compared with the other two groups. The ratio of bax to Bcl-2 mRNA in the combination treatment group was higher than that in the carboplatin-treated group. Finally, phosphorylation of Bcl-2 protein was increased stronger in the combination treatment group compared with the carboplatin-treated group.
CONCLUSIONS: 2-ME promoted the growth inhibitory and apoptosis-inducing effects of platinum-based agents in SKOV3 ovarian cancer cells. The mechanism mediating this effect may be related to the phosphorylation of Bcl-2 protein, which reduces the formation of dimers and, thereby, increases apoptosis. Moreover, 2-ME promoted the mRNA and protein expression of Bax, thereby, increasing the Bax/Bcl-2 expression ratio and activating the mitochondrial apoptosis pathway.