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三氧化二砷诱导人类大肠癌细胞凋亡的分子机制 被引量:19

Molecular mechanism of arsenic trioxide inducing apoptosis in human large intestinal carcinoma cell line
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摘要 目的:明确三氧化二砷(As2O3):注射液对人类大肠癌细胞株的诱导凋亡作用,并探讨其分子机制. 方法:采用四甲基偶氮唑蓝(MTT)比色法、AO/EB荧光染色法、透射电镜观察、DNA电泳、流式细胞术法及免疫组化等方法,系统地观察了As2O3注射液对体外培养的人类大肠癌细胞株LoVo和CoLo-320的生长活力、细胞凋亡、细胞周期及其相关基因表达的影响. 结果:用不同浓度(0.5,1.0,2.0,4.0 mg/L)As2O3作用LoVo和CoLo-320细胞不同时间(24,48,72 h),均能显著抑制其生长(P<0.05),用药后诱导其出现了典型的细胞凋亡的形态学和生化学改变,癌细胞Bcl-2基因表达明显下降,Bax和Fas基因表达显著增强(P<0.01). 结论:As2O3注射液对人类大肠癌细胞具有显著的诱导凋亡作用,这一作用受到多种基因的调控,即Bcl-2基因表达下调,Bax和Fas基因表达上调. AIM: To study the possible apoptosis-inducing effect of arsenic trioxide (As2O3) on the different types of human large intestinal carcinoma cell, and its molecular mechanisms. METHODS: As2O3's action on the cell growth, apoptosis, periodic return and the expression of related genes of the two human large intestinal carcinoma cell lines LoVo and CoLo-320 in vitro was observed by MTT assay, acridine orange (AO)/ethidiumbromide (EB) flurescent staining, electron microscopy detection, DNA gel electrophoresis, flow cytometry, and immunohistochemical staining. RESULTS: After treated by As2O3 at different concentration (0.5, 1.0, 2.0, 4.0 mg/L) for various times (24, 48, 72 h), the human large intestinal carcinoma cell LoVo and CoLo-320 showed strongly inhibitory effect on growth (P<0.05) and also the cells showed typical morphological and biochemical characteristic changes of apoptosis, with bcl-2 gene expression down-regulated, and bax and Fas gene expression up-regulated (P<0.01). CONCLUSION: As2O3 has significant apoptosis-inducing effect on large intestinal carcinoma cells, which is regulated by several genes.
出处 《世界华人消化杂志》 CAS 2004年第7期1550-1554,共5页 World Chinese Journal of Digestology
基金 南京市医学科技发展专项资金资助 No.ZKG0018~~
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