白藜芦醇联合奥沙利铂对人结肠癌细胞恶性生物学行为的抑制作用及机制

Inhibitory Effect and Mechanism of Resveratrol Combined with Oxaliplatin on the Malignant Biological Behavior of Human Colon Cancer Cells

目的:探讨白藜芦醇(Res)联合奥沙利铂(Oxa)对人结肠癌细胞恶性生物学行为的抑制作用及机制。方法:将体外培养结肠癌HCT-116细胞分为Res组、Oxa组、联合组及对照组,分别以100μmoL/L Res、2μmoL/LOxa、100μmoL/L Res+2μmoL/LOxa、等量生理盐水处理,各组分别处理24、36、48 h。采用噻唑蓝(MTT)法检测结肠癌HCT-116细胞增殖抑制情况;采用Transwell小室实验检测结肠癌HCT-116细胞侵袭能力;Wound Healing法检测结肠癌HCT-116细胞迁移能力;采用蛋白免疫印迹法检测结肠癌HCT-116细胞波形蛋白(Vimentin)蛋白表达情况。结果:干预48 h时,Res组、Oxa组及联合组结肠癌HCT-116细胞增殖抑制率分别为(28.41±6.25)%、(36.11±8.47)%、(83.61±12.72)%;干预48 h时,对照组、Res组、Oxa组及联合组结肠癌HCT-116细胞侵袭率分别(97.14±2.81)%、(81.23±4.52)%、(69.84±3.97)%、(37.11±3.58)%;迁移率分别为(68.57±4.02)%、(46.11±3.13)%、(31.25±2.86)%、(18.79±2.21)%;Vimentin蛋白相对表达量分别为0.93±0.14、0.52±0.08、0.31±0.04、0.13±0.02。Res组、Oxa组及联合组结肠癌HCT-116细胞增殖抑制率呈逐渐升高趋势(P<0.05);与对照组比较,Res组、Oxa组及联合组结肠癌HCT-116细胞侵袭率、迁移率和Vimentin蛋白相对表达量降低,且联合组显著低于Res组与Oxa组,差异有统计学意义(P<0.05)。结论:Res与Oxa联合使用具有显著的协同效应,可更有效抑制结肠癌HCT-116细胞增殖,并降低其侵袭和迁移能力,其机制可能与下调Vimentin蛋白表达有关。

Objective:To investigate the inhibitory effect and mechanism of resveratrol(Res)combined with oxaliplatin(Oxa)on the malignant biological behavior of human colon cancer cells.Methods:Colon cancer HCT-116 cells were cultured in vitro.The Res group,the Oxa group,the combination group and the control group were treated with 100μmoL/L Res,2μmoL/L Oxa and 100μmoL/L Res+2μmoL/L Oxa,the same amount of saline,and each group was treated for 24,36,48 h.The inhibition of proliferation of colon cancer HCT-116 cells was detected by MTT assay;Transwell chamber assay was used to detect the invasion ability of colon cancer HCT-116 cells;Wound healing method was used to detect the migration ability of colon cancer HCT-116 cells;The expression of Vimentin protein(vimentin)in colon cancer HCT-116 cells was detected by Western blotting(Wb)method.Results:At 48 h after intervention,the proliferation inhibition rates of HCT-116 cells in the Res group,the Oxa group and the combination group were(28.41±6.25),(36.11±8.47)and(83.61±12.72)%,respectively;At 48 h after intervention,the invasive rates of HCT-116 cells in the control group,the Res group,the Oxa group and the combination group were(97.14±2.81),(81.23±4.52),(69.84±3.97),(37.11±3.58)%,respectively;The mobility rates were(68.57±4.02),(46.11±3.13),(31.25±2.86),and(18.79±2.21)%,respectively;The relative expression levels of Vimentin protein were(0.93±0.14),(0.52±0.08),(0.31±0.04),and(0.13±0.02),respectively.The proliferation inhibition rate of colon cancer HCT-116 cells in the Res group,the Oxa group and the combination group increased gradually(P<0.05);Compared with the control group,the invasion rate,mobility rate and Vimentin protein expression of HCT-116 cells in the Res group,the Oxa group and the combination group significantly decreased,and the combination group was significantly lower than the Res group and the Oxa group(all P<0.05).Conclusion:The combination of Res and Oxa has significant synergistic effect,which can inhibit the proliferation of colon cancer HCT-116 cells and reduce its invasion and migration rate,and its mechanism may be related to the down-regulation of Vimentin protein expression.