【摘要】 目的研究两种PARP-1抑制剂NU1025和AG14361在羟基喜树碱诱导的ECA-109细胞增殖及凋亡中的作用。方法常规培养ECA-109细胞,经HCPT、HCPT和NU1025、HCPT和AG14361处理24h后,采用四甲基偶氮唑蓝比色法观察细胞的增殖情况,通过流式细胞术AnnexinV-FITC/PI双染法分析细胞凋亡情况,通过彗星实验评价DNA损伤程度变化。结果相比于对照组和HCPT组,HCPT和NU1025、HCPT和AG14361联用均显著抑制了细胞的增殖、促进了细胞凋亡、加重了DNA损伤,差异有统计学意义(P<0.05);且HCPT和NU1025联用组较HCPT和AG14361联用组作用更强,两者比较差异有统计学意义(P<0.05)。结论 PARP-1抑制剂NU1025和AG1436均可通过抑制PARP-1活性,进而阻碍细胞DNA损伤修复,增强ECA-109细胞对于抗癌药物HCPT的药敏性,且NU1025具有更低细胞毒性和更强增敏作用的优势,可为食管癌的临床治疗提供一个新的靶点。更多还原

【Abstract】 Objective To explore the effects of two kinds of PARP-1 inhibitors NU1025 and AG14361 on the proliferation and apoptosis of ECA-109 cells induced by the anti-cancer drug hydroxy camptothecin.Methods The ECA-109 cells were routinely cultured and treated with HCPT,HCPT +NU1025 and HCPT+AG14361 for 24 h.Then MTT method was employed to evaluate the proliferation of ECA-109 cells.Flow cytometer annexin V-FITC/PI double staining method was enrolled to analyze the apoptosis the ECA-109 cells,and comet assay was employed to assess the DNA damage content of the ECA109 cells.Results Compared with the control and HCPT treated groups,HCPT+NU1025 and HCPT+AG14361 treatment significantly reduced cell proliferation,increased cell apoptosis and aggravated cell DNA damage(P < 0.05).Conclusion The PARP-1 inhibitor NU1025 and AG14361 both can increase sensitivity of ECA-109 cells in response to HCPT through inhibiting PARP-1 activity,blocked DNA damage and repair.NU1025 has advantage of lower cytotoxicity and higher sensitizing activities and can provide a new target for the clinical treatment of esophageal cancer.更多还原