中国医科大学学报

中国医科大学学报

中国医科大学学报 ›› 2010, Vol. 39 ›› Issue (1): 10–.

• 基础医学 • 上一篇    下一篇

伊立替康抑制人结直肠癌细胞增殖和ATP敏感性钾通道的相关性研究

张依宁; 魏敏杰; 孙明军   

  1. 中国医科大学附属第一医院内镜科; 中国医科大学药学院药理学教研室
  • 出版日期:2010-01-20 发布日期:2013-06-07
  • 通讯作者: 孙明军 E-mail:smjmw@sina.com

The Correlation between the Inhibiting Effects of Irinotecan on Colorectal Cancer Cell Proliferation and ATP -sensitive Potassium Channel

  • Online:2010-01-20 Published:2013-06-07

摘要:

目的检测肿瘤化疗药物伊立替康(CPT-11)对人结直肠癌HCT-116细胞和HT-29细胞的作用,并探讨可能机制。方法用MTT比色法检测细胞增殖;用Transwell法检测细胞侵袭力;用流式细胞术Annexin
      V-FITC/PI双染法检测细胞凋亡;用流式细胞术PI单染法检测细胞周期;用膜片钳方法检测ATP敏感性钾电流(IKATP),并比较药物对两种细胞作用的异同。结果1.064.0μg/ml的CPT-11呈剂量依赖性和时间依赖性抑制HCT-116和HT-29的增殖,CPT-11抑制HCT-116和HT-29细胞增殖作用的半数抑制浓度(IC50)分别为39.3和19.5μg/ml;近似IC50浓度的CPT-11作用48h可使HCT-116和HT-29细胞阻滞于G0/G1期及S期,其中G0/G1期及S期比例分别从27.4%和17.4%上升至95.9%和98.2%,该浓度的CPT-11作用48h还可诱导HCT-116和HT-29细胞凋亡,凋亡率分别从14.8%和9.3%上升到36.9%和27.9%。CPT-11对HCT-116和HT-29细胞的侵袭抑制率分别为40.8%和47.5%。CP...更多T-11可剂量依赖性的降低HCT-116和HT-29细胞膜IKATP水平。结论CPT-11能有效抑制人结直肠癌HCT-116和HT-29细胞增殖和侵袭力、诱导细胞凋亡,且对HT-29细胞的作用较强;CPT-11抑制细胞增殖作用与其抑制细胞膜ATP敏感性钾通道开放相关。

关键词: 伊立替康, HCT-116细胞, HT-29细胞, 细胞增殖

Abstract:

Objective To study the effects of Irinotecan (CPT-11)on human
      colorectal cancer HCT-116 and HT-29 cells and investigate the potential
      mechanisms. Methods The effect of Irinotecan on the proliferation of
      HCT-116 and HT-29 cells was determined by MTT assays. The invasive
      capacity was measured by transwell assays,and the apoptosis of the tumor
      cells was detected by flow cytometry after stained with Annexin-V and PI.
      The difference between the current of ATP-sensitive potassium ion of
      HCT-116 and HT-29 was examined by patch clamp. Results It was found that
      1.0-64.0 μg/ml CPT-11 could inhibit the proliferation and the invasive
      capacity of HCT-116 and HT-29 cells at both dose-and time-dependent
      manner. The IC50 of HCT-116 and HT-29 were 39.3 and 19.5 μg/ml
      respectively. Cytometry showed that the apoptotic rates were increased
      from 14.8% and 9.3% to 36.9% and 27.9% after the treatment of 32.0 μg/ml
      and 16.0 μg/ ml CPT-11,which were close to their IC50. The proportion of
      G0/G1 and S of HCT-116 and HT-29 was enhanced from 27.4% and 17.4% to
      95.9% and 98.2%.Transwell assay indicated that the invasiveness of HCT-116
      and HT-29 was reduced by 40.8% and 47.5%. The patch clamp showed that
      CPT-11 reduced the IKATP of cell membrane at a negative dose-dependent
      manner. Conclusion CPT-11 could have a significant impact on the
      proliferation,invasiveness,cell cycle,and the apoptosis of human
      colorectal cancer cell HCT-116 and HT-29. HT-29 was more sensitive to
      CPT-11 than HCT-116. The inhibitory effect of CPT-11 on cell proliferation
      might be linked to its inhibition of ATP- sensitive potassium channel.

Key words: irinotecan, HCT-116 cell, HT-29 cell, cell proliferation

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