Enhancing Therapeutic Efficacy of Platinum Based Drugs by Pharmacologically Inhibiting PARP in Ovarian Cancer
Dr. Ming Dong
Ovarian cancer is the 5th leading cause of cancer-related death in women. The standard treatment includes platinum-based therapeutics which rely on inducing DNA damage mediated apoptosis. Unfortunately, poly (ADP-ribose) polymerases (PARPs), which play an important role in cellular DNA repair, are over expressed in ovarian cancer cells. PARPs are hypothesized to reduce and delay the effect of chemotherapies that induce DNA damage such as Carboplatin in cancer treatment. In this study, we tested the hypothesis that inhibiting PARP activity would increase efficacy of platinum-based chemotherapeutics. We tested this by evaluating the effect of Carboplatin on OVCAR-3 cells in combination with the PARP inhibitor - Niraparib Tosylate. The effects of Carboplatin with Niraparib Tosylate were analyzed by measuring toxicity (MTT and crystal violet), DNA damage (comet assay and immunoblot analysis) and cell death markers (immunoblot analysis). Our data suggest a synergetic effect of Carboplatin and Niraparib Tosylate by enhancing Carboplatin toxicity to cancer cells.
Gibbs, Synphane, "Enhancing Therapeutic Efficacy of Platinum Based Drugs by Pharmacologically Inhibiting PARP in Ovarian Cancer" (2019). Undergraduate Research and Creative Inquiry Symposia. 173.