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三氧化二砷的抗大肠癌作用及其机制
The effect of As2O3 on induction of apoptosis and inhibition of telomerase activity in colon cancer LS-174T cells
【摘要】 目的观察三氧化二砷(As2O3)对大肠癌LS-174T细胞生长及端粒酶活性的影响。方法As2O3作用于大肠癌LS-174T细胞和裸鼠移植瘤后,采用噻唑盐(MTT)比色法检测结肠癌细胞生长抑制情况,电镜检测细胞超微结构的改变,荧光染色观察细胞核形态变化,流式细胞术(FCM)检测As2O3对细胞周期的影响,聚合酶链反应-酶联免疫反应(PCR-ELISA)试剂盒检测细胞中端粒酶活性变化。结果MTT法显示,随着As2O3浓度的升高,LS-174T细胞存活率明显下降,IC50= 5.23μmol/L。As2O3作用于LS-174T细胞24 h即出现凋亡峰,凋亡细胞的数量随着作用时间增加而增加。As2O3对LS-174T细胞提取液端粒酶活性有一定的抑制作用,对癌细胞端粒酶活性抑制作用随作用时间的延长而加强。从实验动物瘤体积和瘤重两个指标分析,As2O3组与对照组相比具有明显的抑癌作用(P<0.05)。结论经体外、体内实验证实,As2O3对结肠癌LS-174T细胞生长和裸鼠移植瘤均有抑制作用,其抗癌机制可能与诱导细胞凋亡和抑制端粒酶活性有关。
【Abstract】 Objective To study the impact of arsenic trioxide (As2O3) on human colorectal carcinoma LS-174T cells and their activity of telomerase. Methods LS-174T cells and xenograft model of nude mice were treated with As2O3.The inhibitory effect of As2O3 on survival of LS-174T cells was determined by MTT assay. Apoptosis was determined by electron microscopy and fluorescence microscopy. Cell cycle was assessed by flow cytometry. Telomerase activity in LS-174T cells was determined by PCR-ELISA kit. Results With the increasing concentration of As2O3 , the ratio of living cells to dead cells decreased significantly, and the IC50 value was 5. 23μmol/L. Apoptosis curve appeared after 24 h and cells turned to apoptosis in a time-dependent manner. As2O3 inhibited the telomerase activity in cell extraction, obviously in a concentration-dependent and time-dependent manner. Inhibitiory effect of As2O3 on xenograft model of nude mice was observed by tumor volume and weight measurement, showing a significant difference between As2O3 and control groups (P<0.05). Conclusion Both the experiments in vitro and in vivo showed an inhibitory effect of As2O3 on colonrectal cancer S-174T cell growth, probably by induction of apoptosis and inhibition of telomerase activity.
- 【文献出处】 中华肿瘤杂志 ,Chinese Journal of Oncology , 编辑部邮箱 ,2007年06期
- 【分类号】R735.34
- 【被引频次】9
- 【下载频次】74