Abrogation of estrogen receptor signaling augments cytotoxicity of anticancer drugs on caski cervical cancer cells

Background: We have reported that a gene therapy approach, using a dominant-negative estrogen receptor blocker (DN) gene, can cause cell death in cervical cancer cells in vitro. We investigated the mechanisms for enhanced cell killing when DN was combined with cisplatin (CP) and paclitaxel (TX). Materials and Methods: Cells were transduced with DN at 24 h and/or treated with drugs at 48 h, and harvested at 48 and 72 h after transduction. Effects were determined using the MTT cytotoxic, and TUNEL and caspase-3 activity apoptotic assays. Results: Each agent induced cytotoxic and apoptotic effects, and activated caspase-3. In the combined treatments, significant synergistic effects were observed based on the MTT and TUNEL assays, but with antagonistic caspase-3 activation effect. Conclusion: The enhanced cell killing effect was mediated by the initiation of new and multiple mechanisms, particularly via caspase-independent pathways.