Ovarian cancer is still the most deadly cancer among gynecologic tumors, mainly due to the frequent development of resistance to cisplatin that greatly reduces treatment effectiveness. Gaining deeper insight into the molecular basis of this resistance is vital for creating improved therapies. Our RNA sequencing analysis identified MEF2C as a differentially expressed gene associated with the acquisition of cisplatin resistance. We confirmed this observation using RT-qPCR, which revealed significant differences in MEF2C transcript levels between the cisplatin-sensitive A2780 line and its resistant counterpart, A2780cp. Forcing MEF2C expression in the resistant A2780cp cells lowered the cisplatin IC50 value, boosted caspase activation, raised amounts of the pro-apoptotic nuclear receptor NR4A1 (also known as Nur77), and strongly promoted programmed cell death. These outcomes were verified through MTT viability assays, western blotting, and Annexin V/PI flow cytometry. Taken together, the data show that MEF2C levels are reduced in cisplatin-resistant ovarian cancer cells, and that restoring its expression can resensitize the cells to the drug by engaging the intrinsic apoptosis machinery. Clinically, uncovering the drivers of chemoresistance and therapeutically targeting molecules such as MEF2C holds promise for reversing resistance phenotypes, boosting the performance of standard chemotherapy, and ultimately improving patient responses in ovarian cancer management.
