Investigation of cisplatin cellular response in breast cancer via DDB2 and DNA polymerase ETA

In this study, it was aimed to investigate the effect of administration of PNR-7-02 together with cisplatin to MCF-7 breast cancer cells on the expression of genes encoding DDB2 and DNA polymerase η proteins, which are involved in DNA damage responses and cell viability, respectively. Cisplatin is an antineoplastic drug containing a platinum group. It exerts its effect by binding to DNA, inhibiting replication and leading the cell to apoptosis. PNR-7-02 is a chemical molecule derived from indole thiobarbituric acid and developed as an inhibitor of human DNA polymerase η, which is involved in DNA damage tolerance. In this study, cisplatin, PNR-7-02 and their combinations were applied to MCF-7 cells for 24 and 48 hours and their effect on cell viability was determined by MTT assay. The effects of the combined application on cell viability were evaluated by the Chou-Talalay method. DDB2 and DNA polymerase η gene expression analyzes were performed by quantitative real-time polymerase chain reaction. It was observed that given drug combinations at IC50 values were significantly reduced cell viability (p<0.01 for 24 hours, p≤0.005 for 48 hours). Through calculation by the Chou-Talalay method a synergistic effect (CI<1) at low doses of cisplatin when combined with PNR-7-02 was found. When the drugs are administered in doses appropriate to the IC50 for the 24 and 48 hour incubation period, it was found that DDB2 and Pol η gene expressions were increased in single/combined drug-treated cells as compared to the control groups.