Synergetic effect of poly (ADP-ribosyl) polymerase (PARP) inhibitor and cisplatin on ovarian cancer

Abstract

Purpose: To investigate the effect of the combination of poly (ADP-ribosyl) polymerase (PARP) inhibitor, talazoparib (BMN673), and cisplatin on the proliferation and apoptosis of ovarian cancer cells in vitro, and on xenograft tumors of ovarian cancer cells in vivo. Methods: Cell viability was determined by CCK-8 assay, while cell proliferation and cell cycle were assessed using colony formation assay and flow cytometry, respectively. Cell apoptosis was evaluated by flow cytometry and TUNEL assays. Western blot assay was used to measure the expression levels of proliferation- and apoptosis-related proteins. Results: The PARP inhibitor, BMN673, produced a dose-dependent synergistic effect with cisplatin (p < 0.05). Compared with when cisplatin or BMN673 was used alone, the combination of cisplatin and BMN673 significantly inhibited the growth of transplanted tumors (p < 0.05). Immunohistochemical analysis showed that cisplatin and BMN673 treatment increased the number of cells positive for TUNEL, but reduced the population of cells positive for Ki67. Conclusion: Thus, BMN673 and cisplatin are synergistic against ovarian cancer cells, and therefore, should be subjected to further investigations, including clinical trials, to determine the potentials of the combination for the management of ovarian carcinoma. Keywords: PARP inhibitor; Ovarian cancer; Xenografted tumor; Cisplatin