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多聚腺苷二磷酸核糖聚合酶-1抑制剂氟唑帕利对胰腺癌PANC1细胞增殖和迁移的影响

Effect of poly adenosine diphosphate-ribose polymerase-1 inhibitor fluzoparib on the proliferation and migration of pancreatic cancer cell PANC1

摘要目的:探讨多聚腺苷二磷酸核糖聚合酶-1(PARP-1)抑制剂氟唑帕利对胰腺癌PANC1细胞增殖、凋亡和迁移的影响。方法:以常规培养液培养的PANC1细胞为对照组,以含有氟唑帕利培养液培养的PANC1细胞为氟唑帕利组,采用CCK8法检测不同浓度氟唑帕利作用不同时间后对PANC1细胞增殖活性的影响,计算氟唑帕利对PANC1细胞的半抑制浓度(IC 50)。应用流式细胞仪检测氟唑帕利对PANC1细胞凋亡及细胞周期的影响,采用细胞划痕实验和Transwell小室检测PANC1细胞迁移能力。 结果:与对照组比较,随着氟唑帕利浓度的增加以及作用时间的延长,氟唑帕利组PANC1细胞增殖活性显著下降,差异均有统计学意义( P值均<0.05)。氟唑帕利对培养24 h的PANC1细胞的IC 50为0.03 mmol/L。培养24 h后,IC 50氟唑帕利组PANC1细胞凋亡率为(32.19±2.48)%,对照组凋亡率为(21.99±6.30)%,氟唑帕利组较对照组显著增加,差异有统计学意义( P<0.05)。氟唑帕利组G 2/M期细胞比例为(16.28±0.62)%,对照组为(11.64±0.88)%,两组差异有统计学意义( P<0.05)。IC 50氟唑帕利组PANC1细胞迁移率在培养12、24 h时分别为(2.59±1.46)%、(19.76±7.84)%,对照组分别为(27.08±2.17)%、(45.92±3.61)%;氟唑帕利组穿膜细胞数为(348±19)个/10倍视野,对照组为(587±14)个/10倍视野,氟唑帕利组PANC1细胞迁移能力较对照组显著下降,差异有统计学意义( P值均<0.05)。 结论:氟唑帕利在体外可以抑制PANC1的增殖和迁移,促进PANC1凋亡,可能成为治疗胰腺癌的有效药物。

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abstractsObjective:To investigate the effects of poly adenosine diphosphate ribose polymerase-1(PARP-1) inhibitor fluzoparib on proliferation, apoptosis and migration of pancreatic cancer PANC1 cells.Methods:PANC1 cells cultured in conventional culture medium were used as control group, and PANC1 cells cultured in the medium containing fluzoparib were used as fluzoparib group. The effects of fluzoparib with different concentrations on the proliferation of PANC1 cells were detected by CCK8 method, and the half inhibitory concentration (IC 50) of fluzoparib on PANC1 cells was calculated. The effect of fluzoparib on apoptosis and cell cycle of PANC1 cells was detected by flow cytometry, and the migration ability of PANC1 cells was detected by cell scratch test and Transwell chamber. Results:Compared with control group, with the increase of fluzoparib concentration and the prolongation of the action time, the cell proliferation activity of PANC1 in fluzoparib group was significantly decreased, and the differences were statistically significant (all P values <0.05). IC 50 of fluzoparib on PANC1 cells cultured for 24 h was 0.03 mmol/L. After 24 h culture, the IC 50 apoptosis rate of fluzoparib group was (32.19±2.48)%, and the apoptosis rate of control group was (21.99±6.30)%. The former was greatly higher than the latter, and the difference was statistically significant ( P<0.05). The proportion of cells in G 2/M phase was (16.28±0.62)% in the fluzoparib group and (11.64±0.88)% in the control group, and the difference between the two groups was statistically significant ( P<0.05). The migration rates of PANC1 cells in IC 50 fluzoparib group in 12 h and 24 h culture were (2.59±1.46)% and (19.76±7.84)%; and those in control group were (27.08±2.17)% and (45.92±3.61)%, respectively. The number of transmembrane cells was (348±19) cells/10 visual field in the fluzoparib group and (587±14) cells/10 visual field in the control group. The migration ability of PANC1 cells in fluzoparib group was significantly lower than that in control group ( P<0.05). Conclusions:Fluzoparib can inhibit the proliferation and migration of PANC1 cells and promote the apoptosis of PANC1 in vitro, which may be an effective drug for the treatment of pancreatic cancer.

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