RT Journal Article SR Electronic T1 Abrogation of Estrogen Receptor Signaling Augments Cytotoxicity of Anticancer Drugs on CaSki Cervical Cancer Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2181 OP 2187 VO 28 IS 4B A1 MOON Y. HEO A1 SALAMA A. SALAMA A1 NILUFAR KHATOON A1 AYMAN AL-HENDY A1 WILLIAM W. AU YR 2008 UL http://ar.iiarjournals.org/content/28/4B/2181.abstract AB 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. Copyright© 2008 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved