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戴卓睿,毛其芬.二氢青蒿素抑制ATF2的磷酸化提高胃癌细胞对5-氟尿嘧啶的敏感性[J].浙江中西医结合杂志,2018,28(5):
二氢青蒿素抑制ATF2的磷酸化提高胃癌细胞对5-氟尿嘧啶的敏感性
Dihydroartemisinin increases sensitivity of gastric cancer cells to 5-fluorouracil through suppression of ATF2 phosphorylation
投稿时间:2017-11-09  修订日期:2018-03-23
DOI:
中文关键词:  二氢青蒿素  5-氟尿嘧啶  胃癌  ATF2  凋亡
英文关键词:Dihydroartemisinin  5-fluorouracil  gastric cancer  ATF2  apoptosis
基金项目:
作者单位E-mail
戴卓睿* 诸暨市中心医院 mysend@163.com 
毛其芬 浙江省立同德医院  
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中文摘要:
      目的: 探讨中药活性成分二氢青蒿素是否对5-氟尿嘧啶有协同抗胃癌效应并研究其机制。方法: MTT实验检测胃癌细胞系BGC-823的细胞活力;流式细胞术检测BGC-823细胞的凋亡;western blot实验检测BGC-823细胞中ATF2、磷酸化ATF2、Bcl-xl的表达水平及细胞色素c的释放水平和caspase-3的活化水平。结果: 5-氟尿嘧啶联合二氢青蒿素对BGC-823的细胞活力抑制率(67.1±5.5)和凋亡诱导率(37.3±2.9)显著高于5-氟尿嘧啶单治疗组的细胞活力抑制率(18.9±1.5,P<0.05)和凋亡诱导率(9.5±0.9,P<0.05)。5-氟尿嘧啶联合二氢青蒿素治疗组的ATF2磷酸化水平和Bcl-xl表达水平均显著低于5-氟尿嘧啶单治疗组,同时5-氟尿嘧啶联合二氢青蒿素治疗组的细胞色素c释放水平及caspase-3活化水平均显著高于5-氟尿嘧啶单治疗组。另外,5-氟尿嘧啶+二氢青蒿素+ATF2质粒组BGC-823的细胞活力抑制率(26.5±2.1)和凋亡诱导率(14.9±1.1)显著低于5-氟尿嘧啶联合二氢青蒿素组BGC-823的细胞活力抑制率(67.1±5.5,P<0.05)和凋亡诱导率(37.3±2.9,P<0.05)。结论: 二氢青蒿素通过抑制ATF2的磷酸化增强5-氟尿嘧啶对胃癌细胞的杀伤活性。
英文摘要:
      AIM: To investigate the synergistic effect and mechanism of dihydroartemisinin on increasing the cytotoxicity of 5-fluorouracil to gastric cancer. Methods: MTT assay was performed to test the cell viability of BGC-823. Flow cytometry analysis was performed to detect the apoptosis of BGC-823 cells. Western blot analysis was performed to evaluate the expression of ATF2, phosphorylated ATF2 and Bcl-xl, and release of cytochrome c, and the activation of caspase-3 in BGC-823 cells. Results: Cell viability inhibitory rate (67.1±5.5) and apoptotic rate (37.3±2.9) of BGC-823 cells in 5-fluorouracil plus Dihydroartemisinin group was significantly higher than the cell viability inhibitory rate (18.9±1.5, P<0.05) and apoptotic rate (9.5±0.9, P<0.05) of BGC-823 cells in 5-fluorouracil single treatment group. Phosphorylation of ATF and expression of Bcl-xl in the 5-fluorouracil plus dihydroartemisinin group was significantly lower than that in the 5-fluorouracil group. Meanwhile, the release of cytochrome c and activation of caspase-3 in the 5-fluorouracil plus dihydroartemisinin group was significantly higher than that in the 5-fluorouracil single treatment group. In addition, cell viability inhibitory rate (26.5±2.1) and apoptotic rate (14.9±1.1) of BGC-823 in 5-fluorouracil + dihydroartemisinin + ATF2 plasmid group was significantly lower than the cell viability inhibitory rate (67.1±5.5, P<0.05) and apoptotic rate (37.3±2.9, P<0.05) of BGC-823 in 5-fluorouracil + dihydroartemisinin group. Conclusion: Dihydroartemisinin enhanced the cytotoxicity of 5-fluorouracil against gastric cancer through suppression of ATF2 phosphorylation.
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