青蒿素对人胃癌裸鼠移植瘤的生长抑制作用及其机制的研究

Growth inhibition activity and antitumor mechanism of artemisinin on xenografts of human gastric cancer in nude mice

目的:研究青蒿素对人胃癌细胞株SGC-7901裸鼠皮下移植瘤的生长抑制作用及其机制。方法:建立人胃癌裸鼠皮下移植瘤模型,随机分为实验组即青蒿素低剂量组、青蒿素中剂量组和青蒿素高剂量组、空白对照生理盐水组及阳性对照5-FU组,每组5只,分别灌胃连续给药10d,停药后24h处死裸鼠,称取瘤质量,计算抑瘤率,流式细胞仪检测凋亡率,酶标仪检测Caspase-3的活性变化。结果:高、中、低剂量青蒿素组及5-FU组抑瘤率分别为71.4%、47.7%、31.3%及45.2%,与生理盐水组比较差异均有统计学意义P<0.05,青蒿素各实验组抑瘤率与5-FU组相比,高、中剂量组明显比5-FU组强,差异有统计学意义,P<0.05。高、中、低剂量青蒿素组及5-FU组流式细胞仪检测时均出现明显的凋亡分布,凋亡率分别为78.0%、65.9%、45.9%和57.9%,酶标仪检测Caspase-3活性发现随着青蒿素剂量的增加Caspase-3活性逐渐增加,其中高剂量青蒿素活性增加最显著。结论:青蒿素对人胃癌细胞株SGC-7901裸鼠皮下移植瘤有明显的抑制作用,在体内可通过活化Caspase-3诱导细胞凋亡而发挥抗肿瘤作用。

OBJECTIVE：To study the mechanism of different doses of artemisinin on human gastric cancer cell line SGC-7901 implanted under the skin of nude mice in vivo.METHODS：Human gastric cancer cell line SGC-7901 was transplanted to subcutane of nude mice to establish the sample and then randomly divided into five experimental groups,which include an artemisinin-low-dose group,artemisinin-medium-dose group,artemisinin-high-dose group,a blank control saline group and positive control 5-FU group,each of which was composed of five nude mice and then continuously received gavage for 10 days in nude mice,and the nude mice were sacrificed within 24 hours after the withdrawal,with weighting the transplanted tumor and calculating the anti-tumor rate.The apoptotic rate was surveyed by flow cytometry and the activity of Caspase-3 by microplate reader.RESULTS：The inhibition rates of the high-,medium and low-dose artemisinin-based groups and 5-FU group were 71.4%,47.7%,31.3% and 45.2% respectively.Compared with the saline group there were the statistically significant differences （P0.05）.Inhibition rate of each experimental artemisinin group was compared with the 5-FU,and high,medium dose group was significantly than 5-FU,the difference was statisticallg significant （P0.05）.In the high-,medium-and low-dose artemisinin-based groups and 5-FU group,the flow cytometry detection showed the was apparent apoptosis distribution,with the apoptotic rates being 78.0%,65.9%,45.9% and 57.9% respectively,microplate reader detection showed that Caspase-3 activities were increased with the dose of artemisinin,especially in the high-dose artemisinin group.CONCLUSION：Artemisinin can inhibit the tumor growth of human gastric cancer cell line SGC-7901 subcutaneously transplanted in nude mice,through the activation of Caspase-3 inducing cell apoptosis as an anti-tumor effect in vivo.