二氢青蒿素对结肠癌细胞系SW480增殖凋亡的影响

目的:研究二氢青蒿素(DHA)对结肠癌细胞系SW480的增殖、凋亡的作用,初步探讨其机制。方法:采用结肠癌细胞SW480为研究对象,观测不同浓度和作用时间的DHA对细胞作用,MTT噻唑蓝比色法检测对细胞的增殖抑制作用,普通光镜观察细胞形态的变化,分别PI单染及Annexin-V双染法流式细胞术分析细胞周期分布和早期凋亡率的变化,免疫细胞化学检测凋亡抑制蛋白Survivin及效应蛋白Caspase-3表达情况。结果:DHA对SW480细胞增殖有抑制作用且呈浓度和时间依赖性。普通光镜下观察SW480呈典型的凋亡形态学改变。流式细胞仪检测细胞阻滞于G0/G1期,随药物剂量增大G0/G1期比例而逐渐增高,S期比例降低,Annexin-V双染法示早期细胞凋亡率呈明显浓度依赖性升高。免疫细胞化学结果示DHA作用48 h后Survivin表达减弱,而Caspase-3表达增强,呈剂量依赖关系。结论:DHA能显著抑制结肠癌细胞生长,影响细胞周期,诱导细胞凋亡,可能与抑制Survivin蛋白表达,促使Caspase-3表达增强有关。

Effects of Dihydroartemisinin on the Proliferation and Apoptosis of Colon Carcinoma Cell Line SW480

Objective: To observe the effect of Dihydroartemisinin on the proliferation and apoptosis in human colon carcinoma cell line SW480 in vitro and investigate the mechanism.Methods: The inhibition of proliferation of SW480 cells was determined by MTT test.Morphologic changes were observed under optical microscope.Distribution of cell cycle and apoptosis was analyzed using flow cytometry through PI and AnnexinV/PI double-1abeled staining.The expression of cell apoptosis-associated gene protein was detected with immunohistochemical technique.Results: Dihydroartemisinin could inhibit the proliferation of SW480 cells and the inhibition was depended on the exposure dose and time.After treated with Dihydroartemisinin for 48 h,apoptotic cells and morphologic changes could be found under optical microscope.The analysis of cell cycle indicated that Dihydroartemisinin blocked cells at G0/G1 phases,showed an increase of G0/G1 phase and a decrease of S phase.The expression of survivin was down-regulated,and caspase-3 expression was up-regulated.Conclusion: Dihydroartemisinin could inhibit the proliferation of the colon carcinoma cell line SW480 by regulating the cell cycle through arresting cells at G0/G1 phase and inducing apoptosis.The anti-tumor effects of Dihydroartemisinin may be related to the down-regulation of the expression of survivin protein and up-regulation of caspase-3.