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三氧化二砷诱导大肠癌LS-174T细胞凋亡及其对端粒酶活性的影响
The effect of As2O3 on induction of LS-174T cell apoptosis and telomerase activity
【作者】 王锡山; 王贵玉; 徐海涛; 王宽; 刘明; 傅松滨; 耿敬姝; 张岂凡; 董新舒; 赵家宏;
【Author】 Wang Xi-Shan Wang Gui-Yu Xu Hai-Tao Wang Kuan Liu Ming Fu Song-Bin Geng Ye-Mei Zhang Qi-Fan Dong Xin-Shu Zhao Jia-Hong Department of Abdominal Surgery, The third hospital of Harbin Medical University Harbin 150001, P.R. China
【机构】 哈尔滨医科大学附属肿瘤医院;
【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:通过体外细胞培养和裸鼠移植瘤的抑制实验,利用MTT、电镜、FCM和PCR- ELISA等检测方法来观察。结果:MTT法测得随着As2O3浓度的升高,LS-174T细胞存活率明显下降,IC50=5.23 μg/ ml。As2O3作用于LS-174T细胞24h既出现凋亡峰,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。As2O3对裸鼠移植瘤的抑制作用: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)。而与阳性药物 5-FU相比,无显著差异(P>0.05)。结论:As2O3经体外、体内实验证实,对结肠癌LS—174T细胞生长和裸鼠移植瘤均有抑制作用,其抗癌机制主要通过诱导细胞凋亡达到抗癌目的,而其抑制端粒酶活性,可能也是As2O3抗癌机制之一。
【Abstract】 Objective: To study the impact of arsenic trioxide (As2O3) on human colorectal carcinoma cells (LS-174T cell) and the activity of telomerase. Methods: The methods of electron microscope (EMS), PCR-Elisa, flow cytometry (FCM), MTT in vitro and in vivo (LS-174T xenograft model of nude mice) were utilized. Results: With the increasing concentration of As2O3, the ratio of living cells to dead cells decreased significantly, and the IC50 value is 5.23 p. g/ml, Apoptosis curve appeared after 24h, cells turned to apoptosis with time-dependent manner, As2O3 inhibited the activity of telomerase of cell extraction obviously with concentration-dependent and time-dependent manner, Inhibition impact of As2O3 on xenograft model of nude mice: from the two indexes, tumor volume and weight, there was significant difference between As2O3 and control group (p<0.05), there was no difference between As2O3 and 5-Fu group(p>0.05). Conclusion: From the experiment in vitro and in vivo, we can see that As2O3 inhibited LS-174T cell growth mainly by inducing cell apoptosis and inhibition of telomerase activity.
【Key words】 Telomerase inhibitors; As2O3; Colorectal carcinoma; Apoptosis;
- 【会议录名称】 第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议论文集
- 【会议名称】第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议
- 【会议时间】2006-10
- 【会议地点】中国天津
- 【分类号】R735.3
- 【主办单位】中国抗癌协会、中华医学会肿瘤学分会