Investigating Epigenetic Modification as Bio Markers in Ovarian Cancer Cells

Investigating Epigenetic Modification as Bio Markers in Ovarian Cancer Cells

Alvin Sherman Library

Ovarian cancer (OCs) is a one of the leading causes of mortality among gynecological cancers, with approximately 10/100,000 women in the U.S. being diagnosed with the disease. A significant challenge in treating OCs is its inherent resistance to platinum-based chemotherapy drugs, particularly Cisplatin. This study aims to elucidate the mechanisms underlying cisplatin resistance (CR) in ovarian cancer cells by comparing biomarkers of DNA modification between cisplatin-resistant and sensitive ovarian cancer (A2780) cell lines.

Both sensitive and resistant (A2780/A2780-CR) cells were treated with 2 μM of RG-7388, Cisplatin, and CM-272. These drugs are known to act as MDM2 inhibitor, alkylating agent, and DNMT1/G9 inhibitors respectively. Western Blot analysis was employed to investigate the expression of DNMT1 and EZH2 protein levels, which are involved in epigenetic modification of DNA and histones. Our results showed that A2780-CR cells exhibited significantly higher levels of DNMT1 under normal conditions, with a decrease in all drug treatments. Interestingly, A2780 displayed an increase in DNMT1 levels when treated with RG-7388. On the other hand, EZH2 levels decreased significantly with CM272 treatment in both cell lines A2780-CR/A2780, indicating a more promising treatment mechanism after targeting DNMT. Our results suggest that the treatments were effective to some extent in both A2780/A2780-CR cells but also exhibited differences in the pathway-related outcomes. Overall, these findings provide valuable insights into some of existing mechanisms of cisplatin resistance in OCs cells and highlight potential avenues for therapeutic interventions.

(This project was supported by the Royal Dames of Cancer Research Inc. Ft. Lauderdale, Florida).