吲哚美辛联合奥沙利铂对大肠癌细胞生物学行为的影响及机制研究  

Effect of Indomethacin combined with Oxaliplatin on biological behavior of colorectal cancer cells and its mechanism

作　　者：吴维宇[1] 覃岭[1] 张军 高龙[1] WU Weiyu;QIN Ling;ZHANG Jun;GAO Long(Department of Gastroenterology,the First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]成都医学院第一附属医院消化内科,四川成都610500

出　　处：《胃肠病学和肝病学杂志》2018年第12期1367-1371,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：四川省卫生健康委员会普及应用项目(17PJ013)

摘　　要：目的研究抗炎类药物吲哚美辛联合抗癌药物奥沙利铂对人大肠癌细胞SW620生物学行为的影响,并初步探讨其作用机制。方法体外培养人大肠癌细胞株SW620,将细胞随机分为四组进行处理,对照组、吲哚美辛组、奥沙利铂组、吲哚美辛联合奥沙利铂组,采用噻唑蓝(MTT)法检测各组大肠癌细胞增殖抑制情况,采用流式细胞术检测各组大肠癌细胞凋亡情况,采用Transwell实验检测各组大肠癌细胞体外迁移和侵袭能力,采用Western blotting检测各组大肠癌细胞活化的含半胱氨酸的天冬氨酸蛋白水解酶-3(Cleaved Caspase-3)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)的蛋白表达情况。结果与对照组比较,吲哚美辛组和奥沙利铂组大肠癌细胞增殖抑制率显著升高(P<0.05)。与单用药组比较,联合用药组大肠癌细胞增殖抑制率、凋亡率、迁移和侵袭能力均明显升高,细胞中Cleaved Caspase-3蛋白表达量明显升高,MMP-2、MMP-9蛋白表达量明显降低,差异有统计学意义(P<0.05)。结论吲哚美辛联合奥沙利铂可协同增强对大肠癌细胞增殖、侵袭和转移抑制作用,协同诱导细胞凋亡,其作用机制可能与吲哚美辛、奥沙利铂调控细胞中Cleaved Caspase-3、MMP-2、MMP-9蛋白表达有关。Objective To study the effect of Indomethacin combined with anticancer drug Oxaliplatin on the biological behavior of human colorectal cancer cell line SW620,and to explore its mechanism.Methods Human colon cancer cell line SW620was cultured in vitro.The cells were randomly divided into four groups:control group,Indomethacin group, Oxaliplatin group,Indomethacin combined with Oxaliplatin group.The proliferation inhibition of colorectal cancer cells was detected by MTT method.The apoptosis of colorectal cancer cells was detected by flow cytometry.Transwell assay was used to detect the migration and invasion ability of colorectal cancer cells in vitro.Western blotting was used to detect the expressions of caspase-containing caspase-3(Cleaved caspase-3),matrix metalloproteinase-2(MMP-2)and matrix metal-loproteinase-9(MMP-9)proteins activated by cancer cells.Results Compared with the control group,the inhibition rate of colorectal cancer cells in the Indomethacin group and the Oxaliplatin group was significantly increased (P <0.05). Compared with the single-agent groups,the proliferation inhibition rate,apoptosis rate,migration and invasion ability of colorectal cancer cells in the combination group were significantly increased,and the expression of Cleaved Caspase-3 protein was significantly increased in the cells.The expressions of MMP-2and MMP-9were significantly reduced,and the differences were statistically significant (P <0.05).Conclusion Indomethacin combined with Oxaliplatin can synergistically enhance the growth,invasion and metastasis of colorectal cancer cells,and synergistically induce apoptosis. The mechanism may be related to expressions of Cleaved Caspase-3,MMP-2,MMP-9proteins in Indomethacin and Oxaliplatin-regulated cells.

关 键 词：吲哚美辛 奥沙利铂 大肠癌细胞 生物学行为 

分 类 号：R735.34[医药卫生—肿瘤]