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华宏军,叶晓华,陈媛,陈燕萍.青蒿琥酯协同5-氟尿嘧啶杀伤胰腺癌细胞及机制研究[J].浙江中西医结合杂志,2018,28(8):
青蒿琥酯协同5-氟尿嘧啶杀伤胰腺癌细胞及机制研究
Mechanism and synergistic effect of artesunate on 5-fluorouracil-induced cytotoxicity against pancreatic cancer
投稿时间:2018-03-06  修订日期:2018-05-08
DOI:
中文关键词:  青蒿琥酯  survivin  5-氟尿嘧啶  胰腺癌  凋亡
英文关键词:artesunate  survivin  5-fluorouracil  pancreatic cancer  apoptosis
基金项目:
作者单位E-mail
华宏军 金华市中心医院 myzhuhui@163.com 
叶晓华 金华市中心医院  
陈媛 金华市中心医院  
陈燕萍 金华市中心医院  
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中文摘要:
      目的 探讨中药活性成分青蒿琥酯对胰腺癌5-氟尿嘧啶化疗的辅助治疗作用并研究其机制。方法: MTT法检测青蒿琥酯和5-氟尿嘧啶对胰腺癌细胞系Capan-2的杀伤活性。Western blot实验检测Capan-2细胞中survivin的表达水平和细胞色素c、凋亡诱导因子从线粒体中的释放水平。流式细胞术检测Capan-2细胞的线粒体膜电位和凋亡率。结果: 青蒿琥酯对5-氟尿嘧啶有协同作用,青蒿琥酯联合5-氟尿嘧啶组Capan-2的细胞活力抑制率(68.5±5.9)%和凋亡率(37.9±3.2)%显著高于5-氟尿嘧啶单处理组Capan-2的细胞活力抑制率(20.7±2.1)%(P<0.05)和凋亡率(11.3±1.5)%(P<0.05)。青蒿琥酯处理显著抑制Capan-2细胞中survivin的表达。青蒿琥酯联合5-氟尿嘧啶组Capan-2细胞的线粒体膜电位明显低于5-氟尿嘧啶单处理组。青蒿琥酯联合5-氟尿嘧啶组Capan-2细胞的细胞色素和凋亡诱导因子释放水平均明显高于5-氟尿嘧啶单处理组。青蒿琥酯发挥对5-氟尿嘧啶的协同作用依赖于survivin的抑制,青蒿琥酯+5-氟尿嘧啶+survivin质粒组Capan-2的细胞活力抑制率(26.8±2.5)%和凋亡率(14.5±1.7)%显著低于青蒿琥酯+5-氟尿嘧啶组Capan-2的细胞活力抑制率(68.5±5.9)%(P<0.05)和凋亡率(37.9±3.2)%(P<0.05)。结论: 青蒿琥酯抑制survivin的表达发挥对5-氟尿嘧啶的协同抗胰腺癌活性。
英文摘要:
      objective To explore the adjuvant effect and mechanisms of artesunate on 5-fluorouracil-based chemotherapy in pancreatic cancer. Methods MTT assay was performed to evaluate the cytotoxicity of artesunate and 5-fluorouracil against Capan-2 cells. Western blot analysis was conducted to detect the expression of survivin and release of cytochrome c and apoptosis inducing factor from mitochondria into cytoplasm. Flow cytometry analysis was performed to detect the mitochondrial membrane potential and apoptosis of Capan-2. Results Artesunate acted synergistic effect on 5-fluorouracil. Combination with artesunate and 5-fluorouracil induced higher cell viability inhibitory rate (68.5±5.9)% and apoptotic rate (37.9±3.2)% compared to the 5-fluorouracil single treatment group’s cell viability inhibitory rate (20.7±2.1)%(P<0.05) and apoptotic rate (11.3±1.5)%(P<0.05). Mitochondrial membrane potential of Capan-2 in artesunate plus 5-fluorouracil group was obviously lower than the 5-fluorouracil single treatment group. Release of cytochrome c and apoptosis inducing factor in artesunate plus 5-fluorouracil group was stronger than the 5-fluorouracil single treatment group. Artesunate acted synergistic effect on 5-fluorouracil was dependent on the inhibition of survivin. Artesunate+5-fluorouracil+survivin plasmid group induced lower cell viability inhibitory rate (26.8±2.5)% and apoptotic rate (14.5±1.7)% compared to the Artesunate+5-fluorouracil group’s cell viability inhibitory rate (68.5±5.9)%(P<0.05) and apoptotic rate (37.9±3.2)%(P<0.05). Conclusion Artesunate acted synergistic effect on 5-fluorouracil-induced cell death in pancreatic cancer was dependent on the inhibition of survivin.
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