PARP-1抑制剂对细胞周期特异性毒物诱导的骨肉瘤细胞凋亡的影响  

Effect of PARP inhibitor on apoptosis of osteosarcoma cells induced by a cell cycle-specific toxicant

作　　者：姚志莹 李蕾 张昱 

机构地区：[1]江西省南昌市卫生学校,江西南昌330006

出　　处：《中国病原生物学杂志》2014年第1期40-42,共3页Journal of Pathogen Biology

摘　　要：目的探讨PARP抑制剂BMN-673在替尼泊苷(VM-26)诱导的MG-63细胞增殖及凋亡中的作用。方法采用常规方法培养MG-63细胞,经BMN-673和(或)ABT-888处理12h后,采用MTT比色法分析细胞的活力,采用流式细胞术Annexin V-FITC/PI双染法分析细胞凋亡水平,采用ELISA试验与细胞中半胱氨酸蛋白酶活性。结果 BMN-673与VM-26联用组、对照组及VM-26单独使用组细胞活力分别为58.00%、97.00%和77.00%,差异有统计学意义(P<0.05);细胞凋亡水平分别为42.00%、3.00%和23.00%,差异有统计学意义(P<0.01);细胞中Caspase-3、Caspase-6和Caspase-9活性分别为12.15%、8.28%和9.09%,5.25%、2.51%和3.12%,2.89%、0和0.98%,差异有统计学意义(P<0.05)。结论 PARP抑制剂BMN-673可通过抑制PARP-1活性,进而抑制细胞DNA损伤修复,来增强MG-63细胞对抗癌药物VM-26的药敏性,为骨肉瘤化疗药物的临床研究了提供新的思路。Objective To discuss the effect of PARP inhibitor BMN 673 on proliferation and apoptosis of MG-63 cells induced with teniposide （VM-26）. Methods Conventionally cultured MG-63 cells were treated with BMN 673 and/or ABT-888 for 12h and an MTT colorimetric assay was performed to analyze cell activity. Flow cytometry （annexin V FITC/PI double staining） was used to analyze the level of apoptosis. Cysteine protease activity was evaluated using ELISA. Results Cells treated with BMN 673 had cell activity of 58.00%, cells treated with BMN-673 and VM-26 had cell activity of 97.00%, and a control group treated with VM 26 alone had cell activity of 77.00%. Differences in cell ac- tivity were statistically significant （P〈0.05）. The level of apoptosis was 42.00% in cells treated with BMN-673, 3.00Y00 in cells treated with BMN 673 and VM-26, and 23.00% in the control group. Differences in the level of apoptosis were statistically significant （P〈0.01）. Levels of Caspase-3, Caspase-6, and Caspase-9 activity were 12. 15%, 8.28%, and 9.09% in cells treated with BMN-673, 5.25%, 2. 51%, and 3. 12% in ceils treated with BMN-673 and VM26, and 2.89%, 0%, and 0.98% in the control group. Differences in the levels of Caspase-3, Caspase-6, and Caspase 9 activity were statistically significant （P〈0.05）. Conclusion The PARP inhibitor BMN 673 may inhibit PARP-1 activity and thus inhibit the repair of injury to cellular DNA, enhancing the susceptibility of MG-63 cells to the anti-cancer drug VM 26. This may provide a new avenue for clinical research on chemotherapy drugs to fight osteosarcoma.

关 键 词：骨肉瘤 替尼泊苷 PARP抑制剂 BMN-673 半胱氨酸蛋白酶 

分 类 号：R392[医药卫生—免疫学]