PARP-1在脱氧胆酸钠促结肠癌细胞增殖中的作用

结肠癌的发生与肠腔内脱氧胆酸引起的DNA损伤有关,聚腺苷二磷酸核糖聚合酶-1（PARP-1）对DNA损伤具有修复作用.目的：探讨PARP-1在脱氧胆酸钠促结肠癌细胞增殖中的作用及其可能机制.方法：选用不同浓度的脱氧胆酸钠、PARP-1抑制剂5-氨基异喹啉酮（5-AIQ）或两者联合分别作用于人结肠腺癌细胞株HT-29.MTT实验检测细胞增殖情况,流式细胞仪检测细胞周期和细胞凋亡,免疫细胞化学染色检测环氧合酶-2（COX-2）、caspase-3、PARP-1蛋白表达.结果：10～50 μmol/L脱氧胆酸钠能促进HT-29细胞增殖,增加COX-2、PARP-1蛋白表达,减低caspaae-3蛋自表达.100μmol/L 5-AIQ单独作用对HT-29细胞增殖无明显影响,但能减低COX-2、PARP-1蛋白表达.与单独作用相比,10μmol/L脱氧胆酸钠与100 μmol/L 5-AIQ联合能显著抑制HT-29细胞生长,阻滞细胞周期,诱导细胞凋亡,COX-2、PARP-1蛋白表达减低,caspase-3蛋白表达无明显变化.结论：COX-2与PARP-1在脱氧胆酸钠促结肠癌细胞增殖的过程中可能存在相互作用,PARP-1抑制剂5-AIQ可能用于预防脱氧胆酸诱发的结肠癌.

Effect of PARP-1 on Proliferation of Colon Cancer Cells Induced by Sodium Deoxycholate

Background： It is reported that DNA damage induced by colonic luminal deoxycholic acid is involved in colon carcinogenesis, and DNA damage can be repaired by poly（ADP-ribose） polymerase-1 （PARP-1）. Aims： To investigate the effect of PARP-1 on proliferation of colon cancer cells induced by sodium deoxycholate and its potential mechanism. Methods： Human colon adenocarcinoma cell line HT-29 was treated with different concentrations of sodium deoxycholate, 5-aminoisoquinolinone （5-AIQ, an inhibitor of PARP-1） and their combination, respectively. The proliferation activity of HT-29 cells was measured by MTT assay, the cell cycle and apoptosis were analyzed by flow cytometry, and the protein expressions of eyclooxygenase-2 （COX-2）, caspase-3 and PARP-1 were determined by immunocytochemical stain. Results： Sodium deoxycholate （10-50 μmol/L） enhanced the proliferation of HT-29 cells, increased COX-2 and PARP-1 expressions and decreased easpase-3 expression, while 5-AIQ （100 μmol/L） inhibited the expressions of COX-2 and PARP-1 but had no obvious effect on cell proliferation. Compared with sodium deoxycholate （10 μmol/L） alone, co- administration of sodium deoxycholate （10 μmol/L） and 5-AIQ （100 μmol/L） suppressed the proliferation of HT-29 cells, arrested cell cycle and induced apoptosis, concomitantly with a decrease of COX-2 and PARP-1 expressions and an unchanged caspase-3 expression. Conclusions： There might be an interaction between COX-2 and PARP-1 in the process of proliferation of colon cancer cells induced by sodium deoxycholate. 5-AIQ, the inhibitor of PARP-1, might be a promising agent in preventing colon cancer induced by deoxycholic acid.