β-二氢青蒿素-大黄素复合物对人胃癌细胞株SGC-7901增殖的影响

Effects of β-dihydroartemisinin-emodin on the inhibition of proliferation in human gastric cancer SGC-7901 cells

目的探讨β-二氢青蒿素-大黄素复合物抑制人胃癌SGC-7901细胞增殖,促进其凋亡的作用及机制。方法用MTT比色法检测β-二氢青蒿素-大黄素复合物对SGC-7901细胞的抗增殖及细胞毒作用;利用流式细胞仪分析复合物作用前后SGC-7901细胞周期分布及凋亡率的改变;应用免疫细胞化学染色法检测蛋白CyclinD1和Ki-67的表达变化。结果(1)MTT结果显示,β-二氢青蒿素-大黄素复合物对SGC-7901细胞抑制作用显著,且呈浓度-时间依赖性(P<0.05);(2)流式细胞仪检测分析出:实验组的细胞增殖被阻滞于G0/G1期、且凋亡率升高,均呈浓度梯度趋势(P<0.05);(3)免疫细胞化学染色结果显示:实验组中Ki-67和CyclinD1的阳性表达率明显降低,且具有浓度依赖性(P<0.05)。结论β-二氢青蒿素-大黄素复合物可以抑制人胃癌SGC-7901细胞的增殖,促进其凋亡,并且呈时效和量效关系;其作用机制可能与影响细胞周期有关,且药物浓度越高,下调作用越明显。

Objective To explore whether β-dihydroartemisinin-emodin could inhibit the proliferation of SGC-7901 cells,and if its mechanism is related to the blockage of cell cycle.Methods The anti-proliferation and cytotoxic effects of β-dihydroartemisinin-emodin on SGC-7901cells were studied by MTT colorimetric assay.Flow cytometry were performed to analyze cell cycle distribution.The expression of cell cycle related protein CyclinD1and proliferating cell nuclear antigen Ki-67were detected with the immunocytochemical staining.Results①Results measured by MTT colorimetric assay:all of five drugs,including hydroartemisinin,emodin,emodin-butanediol,α-dihydroartemisinin-emodin and β-dihydroartemisinin-emodin,had the anti-proliferation effect with different inhibition ratios of SGC-7901cells(P<0.05).②Detection of cell cycle distribution:the amount of cells in experimental group at G0/G1phase increased obviously,and cells at G2/M phase and S phase decreased with statistically significance(P<0.05).③Results of immunocytochemistry staining:the expression of cell cycle related protein CyclinD1and proliferating cell nuclear antigen Ki-67in experimental group decreased with statistically significance(P<0.05).Conclusion The effect of β-dihydroartemisinin-emodin on the inhibition of proliferation in SGC-7901cells had dose-effect relationship and time-response relationship.The effect of β-dihydroartemisinin-emodin on the inhibition of proliferation in SGC-7901cells was related to the down-regulated expression of Ki-6,and the down-regulatory effect was more obviously with the increasing of drug concentration.