双氢青蒿素联合奥沙利铂对人结肠癌HCT116细胞的增殖及凋亡的影响

Effects of Dihydroartemisinin and Oxaliplatin on Proliferation and Apoptosis of Human Colon Cancer HCT116 Cells

研究双氢青蒿素(DHA)与奥沙利铂(L-OHP)联合对人结肠癌HCT116细胞的增殖及凋亡的影响,初步探讨凋亡的作用机制。运用MTT法检测不同浓度DHA、L-OHP及DHA与L-OHP联合对HCT116细胞的抑制作用,计算DHA与L-OHP是否发挥协同作用。实验结果显示DHA与L-OHP均对HCT116细胞增殖有抑制作用,二者联合在一定浓度下发挥协同作用。应用Annexin V-FITC/PI双染检测药物联用后细胞凋亡情况,结果显示联合组比DHA组和L-OHP组凋亡率提高(P <0. 01)。通过检测凋亡相关蛋白Bcl-2及Bax含量及casepase-3、casepase-8活性发现,与单药组比较DHA、L-OHP联合组Bcl-2/Bax降低,casepase-3、casepase-8活性提高(P <0. 01)。研究结果表明DHA与奥沙利铂联合能够显著抑制结肠癌HCT116细胞的增殖,在一定浓度下发挥协同作用,且能诱导细胞凋亡,其机制可能与加重DNA损伤,下调Bcl-2/Bax,激活casepase-3、casepase-8有关。

The effects of dihydroartemisinin(DHA)combined with oxaliplatin(L-OHP)on the proliferation and apoptosis of human colon cancer HCT116cells were studied,and the mechanism of apoptosis was discussed.The effects of DHA,L-OHP and DHA combined with L-OHP in different concentrations on HCT116cells were detected by MTT.The results showed that DHA and L-OHP inhibited the proliferation of HCT116cells.Dihydroartemisinin and oxaliplatin played a synergistic effect at a certain concentration.AnnexinV-FITC/PI double staining was used to detect the apoptosis,and the results showed that the apoptosis rate of the combination group was higher than that of DHA group and L-OHP group(P<0.01).In addition,it was found that the apoptosis-related proteins Bcl-2/Bax was decreased and the casepase-3and casepase-8activity was increased in the combined group compared with the single drug group(P<0.01).The results showed that the combination of dihydroartemisinin and oxaliplatin could significantly inhibit the proliferation of colon cancer HCT116cells,exert a synergistic effect at a certain concentration,and induce apoptosis,which may be related to enhance DNA damaged,down-regulation of Bcl-2/Bax and activated casepase-3,casepase-8.