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• 基础医学 • 上一篇    下一篇

三氧化二砷对人大肠癌细胞端粒酶活性及细胞凋亡的影响

徐 丹1,杨幼林1,王彦君2   

  1. 1. 哈尔滨医科大学附属第一医院消化内科,黑龙江 哈尔滨 150001;2. 吉林大学第一医院消化内科,吉林 长春 130021
  • 收稿日期:2007-10-15 修回日期:1900-01-01 出版日期:2008-03-28 发布日期:2008-03-28
  • 通讯作者: 王彦君

Effect of arsenic trioxide on telomerase activity and apoptosis of human colon cancer cell Line

XU Dan1,YANG You-lin1,WANG Yan-jun2   

  1. 1.Department of Digestive Diseases,First Affiliated Hospital, Harbin Medical University,Harbin 150001,China;2. Department of Digestive Diseases,First Hospital,Jilin University,Changchun 130021,China
  • Received:2007-10-15 Revised:1900-01-01 Online:2008-03-28 Published:2008-03-28
  • Contact: WANG Yan-jun

摘要: 目的:探讨三氧化二砷(As2O3)对人大肠癌细胞株 CCL-187 端粒酶活性及细胞凋亡的影响。方法:CCL-187 细胞分为对照组、1.0 μmol•L-1As2O3 组和 2.5 μmol•L-1As2O3 组,共同孵育1~6 d。MTT 法计算细胞生长抑制率,电镜下观察细胞形态学变化,RT-PCR 法检测细胞端粒酶 hTERT-mRNA 的表达,TRAP-PCR-ELISA 法检测细胞端粒酶活性。结果:1.0 μmol•L-1 As2O3 组细胞分化明显,2.5 μmol•L-1As2O3 组出现细胞凋亡。同时2组端粒酶 hTERT-mRNA 的表达均下调,端粒酶活性降低,且具有时间依赖性,与对照组比较差异有显著性(P<0.01 或 P<0.05);2.5 μmol•L-1 As2O3 组与 1.0 μmol•L-1 As2O3 组比较差异也有显著性(P<0.01)。细胞生长抑制率与细胞端粒酶 hTERT-mRNA 的表达呈负相关(1.0 μmol•L-1 As2O3 组 r=-0.803,P<0.01;2.5 μmol•L-1 As2O3 组 r=-0.697,P<0.01),与端粒酶活性的下调呈负相关(1.0 μmol•L-1 As2O3 组 r=-0.836,P<0.01;2.5 μmol•L-1 As2O3 组 r=-0.792,P<0.01);细胞端粒酶 hTERT-mRNA 的表达与细胞端粒酶活性呈正相关(1.0 μmol•L-1 As2O3 组 r=0.956,P<0.01;2.5 μmol•L-1 As2O3 组 r=0.988,P<0.01)。结论:As2O3 对 CCL-187 细胞有促进分化及诱导凋亡的作用,其机制可能是下调细胞端粒酶 hTERT-mRNA 的基因表达,从而抑制端粒酶的活性。

关键词: 细胞凋亡, 端粒酶, 端粒

Abstract: Objective Abstract:Objective To explore the effects of arsernic trioxide (As2O3) on telomerase activity and cellular apoptosis of human colon cancer cell line CCL-187.Methods CCL-187 cells were divided into control group,1.0 μmol•L-1As2O3 group and 2.5 μmol•L-1As2O3 group,all groups were cultivated for 1 to 6 d.The inhitory rate of cell growth was detected by MTT assay.The morphologic changes of CCL-187 cells were observed under electron microscope.The expression of hTERT at mRNA level was analyzed by RT-PCR.Telomerase activity was determined by TRAP-PCR-ELISA.Results The differentiation of cells was found in 1.0 μmol•L-1 As2O3 group,but apoptosis in 2.5 μmol•L-1 As2O3 group,and at the same time ,the telomerase activity was reduced and the hTERT-mRNA expression was downregulate in 1.0 μmol•L-1 As2O3 group and 2.5 μmol•L-1 As2O3 group in a time-dependent manner.There were significant differences compated with control group(P<0.01 or P<0.01);there were also significant differences between 2.5 μmol•L-1 As2O3 group and 1.0 μmol•L-1 As2O3 group(P<0.01).The inhibitory rate of cell growth was closely negatively correlated with the downregulation of hTERT-mRNA(1.0 μmol•L-1 As2O3 group,r=-0.803,P<0.01;2.5 μmol•L-1 As2O3 group,r=-0.697,P<0.01) and the reduction of telomerase activity(1.0 μmol•L-1 As2O3 group,r=-0.836, P<0.01;2.5 μmol•L-1As2O3 group,r=-0.792,P<0.01).The reduction of telomerase activity was closely correlated with the downregulation of the hTERT-mRNA(1.0 μmol•L-1 As2O3 group,r=0.956,P<0.01; 2.5 μmol•L-1 As2O3 group,r=0.988,P<0.01).Conclusion As2O3 can induce differentiation and apoptosis of CCL-187 cells.Its mechnism may be ralated to reducting the telomerase activity through downregulation of the hTERT-mRNA expression.

Key words: apoptosis, telomerase, telomere

中图分类号: 

  • R735.34