Effect of polyadenyl diphosphate ribose polymerase 1 inhibitor on the sensitivity of As2O3 in treating renal cancer cells in vitro study

Objective To explore the effect of inhibition of poly (ADP-ribose) polymerase-1 (PARP-1) (AG14361) on the sensitivity of cells to arsenic trioxide (As2O3) in treating renal cancer cells. Methods Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, colony formation assay, single cell gel electrophoresis and micronucleus assay, flow cytometry were used to detect the cytotoxicity, genotoxicity and apoptosis of As2O3 combined with AG14361 on renal cancer cells. Results The colony formation rate [Combination group vs. As2O3 group: OS-RC-2, (43.23±3.12)% vs. (62.35±2.69)%; 786-O, (36.23±3.12)% vs. (58.31±2.42)%; HK-2, (56.32±3.46)% vs. (68.92±3.12)%], The difference was statistically significant (P<0.05); Single cell gel electrophoresis and micronucleus test showed that DNA and chromosome damage increased in the combination group compared with As2O3 group, and the difference was statistically significant (P<0.05). Flow cytometry shows, the combination group significantly enhanced the apoptotic rate of renal cancer cells compared with the As2O3 group [OS-RC-2, (59.90±86.75)% vs. (17.00±3.61)%; 786-O, (41.47±4.11)% vs. (15.17±1.99)%; HK-2, (30.43±4.92)% vs. (13.17±3.26)%]. Conclusion AG14361 has a sensitizing effect on the killing effect of As2O3-induced renal cancer cells, and its mechanism may be through inhibition of single-double-strand damage repair, which in turn causes chromosome damage. Key words: Renal cancer cells; As2O3; AG14361; Sensitizing