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

中华实验外科杂志 Pub Date : 2019-12-08 DOI:10.3760/CMA.J.ISSN.1001-9030.2019.12.006

Qian Cheng, Dafei Chai, Gang Wang, Zheng Lu, J. Bai

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Abstract

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

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聚二磷酸腺苷核糖聚合酶1抑制剂对As2O3治疗肾癌症细胞敏感性的影响

目的探讨抑制多（ADP-核糖）聚合酶-1（PARP-1）（AG14361）对癌症细胞对三氧化二砷（As2O3）敏感性的影响。方法采用甲基噻唑二苯基溴化四氮唑（MTT）法、集落形成法、单细胞凝胶电泳法、微核法、流式细胞术等方法检测As2O3联合AG14361对癌症细胞的细胞毒性、遗传毒性和凋亡。结果集落形成率[联合用药组与As2O3组相比：OS-RC-2，（43.23±3.12）%与（62.35±2.69）%；786-O，（36.23±3.12）%与（58.31±2.42）%；HK-2，（56.32±3.46）%vs（68.92±3.12）]，差异有统计学意义（P<0.05）；单细胞凝胶电泳和微核试验显示，与As2O3组相比，联合用药组DNA和染色体损伤增加，差异有统计学意义（P<0.05）。流式细胞仪显示，与As2O3组相比，联合用药组明显提高了肾癌症细胞的凋亡率[OS-RC-2，（59.90±86.75）%对（17.00±3.61）%；786-O，（41.47±4.11）%对（15.17±1.99）%；HK-2，（30.43±4.92）%对对（13.17±3.26）%]，其机制可能是通过抑制单双链损伤修复，进而引起染色体损伤。关键词：癌症肾细胞；As2O3；AG14361；致敏

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中华实验外科杂志

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