Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to exhibit antitumor activities. Among the very well-known oncogenes in breast cancer is zinc finger protein 703 (ZNF703) and cyclooxygenase-2 (COX-2). Numerous reports indicate a direct link among apoptosis resistance, chemotherapy resistance, and increased expression of ZNF703. In the present study, the expression level of ZNF703 was compared in human breast cancer tissue, healthy breast tissue, and MCF-7 breast cancer cell line by a real-time PCR. We also investigated the inhibitory effect of anti-ZNF703 RNAi interference (RNAi) and ibuprofen, either individually or in combination, on MCF-7 cell survival and apoptosis. Results showed a 93.3% and fourfold increase in the expression of ZNF703 in breast cancer tissue and MCF-7 cell line, respectively. Ibuprofen inhibited the viability of MCF-7 cells in a concentration-dependent manner. Ibuprofen alone or in combination with anti-ZNF703 RNA reduced the expression of ZNF703, induced apoptosis, reduced mitochondrial membrane potential, and elevated BAX and LC3A in MCF-7 cells. Our results show that the combination of ibuprofen and anti-ZNF703 siRNA is more effective in promoting apoptosis than each treatment alone. We report that the combination of anti-ZNF703 RNAi with ibuprofen as the inhibitor of COX-2 is highly effective in inhibiting MCF-7 as a breast cancer cell line and shows therapeutic potential for breast cancer.
Keywords: RNAi; ZNF703; apoptosis; cancer; ibuprofen; molecular targeted therapy.
© 2019 International Union of Biochemistry and Molecular Biology, Inc.