解剖学报 ›› 2018, Vol. 49 ›› Issue (1): 70-74.doi: 10.16098/j.issn.0529-1356.2018.01.011

• 肿瘤生物学 • 上一篇    下一篇

双氢青蒿素对人胰腺癌细胞系增殖和凋亡的影响

朱文赫 许娜 徐俊杰 张红 李妍 吕士杰 张巍*   

  1. 吉林医药学院生物化学教研室,吉林 吉林 132013
  • 收稿日期:2017-05-08 修回日期:2017-07-05 出版日期:2017-02-06 发布日期:2018-02-06
  • 通讯作者: 张巍 E-mail:jlmmczw@163.com
  • 基金资助:
    吉林省卫计委青年科研课题

Effects of dihydroartemisinin on proliferation and apoptosis of human pancreatic cancer cell line

ZHU Wen-he XU Na XU Jun-jie ZHANG Hong LI Yan Lü Shi-jie ZHANG Wei*   

  1. Deptment of Biochemistry, Jilin Medical College, Jilin Jilin 132013, China
  • Received:2017-05-08 Revised:2017-07-05 Online:2017-02-06 Published:2018-02-06
  • Contact: ZHANG Wei E-mail:jlmmczw@163.com

摘要:

目的 探讨双氢青蒿素对人胰腺癌细胞(PANC-1)增殖活性及凋亡的影响,及其作用机制。 方法 30、60、120、240和480 μmol/L双氢青蒿素作用PANC-1 48 h后,采用MTT法检测双氢青蒿素对PANC-1增殖活性的影响,流式细胞术检测其细胞周期和凋亡的变化,Western blotting检测细胞内周期相关蛋白cyclin B1、Cdk1、p21及凋亡相关蛋白Bcl-2, Bax, Caspase-3, Caspase-9和细胞色素C(Cyto C)蛋白表达变化。 结果 MTT实验结果表明,30~480 μmol/L双氢青蒿素对PANC-1增殖活性具有明显的抑制作用(P<0.05)。流式细胞仪检测结果显示,双氢青蒿素可以使PANC-1细胞周期阻滞于G2/M期,并诱发PANC-1细胞发生凋亡,且随药物浓度呈现升高趋势(P<0.05)。Western blotting结果显示,双氢青蒿素作用后周期相关蛋白Cdk1和Cyclin B1蛋白表达降低,而P21蛋白表达升高。凋亡相关蛋白Bcl-2蛋白表达下调,Bax蛋白表达上调,Bax/Bcl-2蛋白表达比例升高, cleaved Caspase-3,cleaved Caspase-9和Cyto C蛋白表达升高。 结论 双氢青蒿素能抑制PANC-1增殖并诱发细胞凋亡,其凋亡机制可能与线粒体途径相关。

关键词: 双氢青蒿素, 胰腺癌, G2/M期阻滞, 免疫印迹法,

Abstract:

Objective To investigate the effect of dihydroartemisinin on proliferation and apoptosis of human pancreatic cancer cell (PANC-1) and explore its mechanism.Methods After PANC-1cells treated with 30, 60, 120, 240 and 480 μmol/L dihydroartemisinin for 48 hours, MTT assay was used to detect the proliferation effect of dihydroartemisinin on PANC-1 cells. The cell cycle and apoptosis were detected by flow cytometry. The expressions of cyclin B1, Cdk1, p21 and apoptosis related protein Bcl-2, Bax, Caspase-3, Caspase-9 and cytochrome C(Cyto C) were detected by Western blotting. Results MTT result showed that the proliferation of PANC-1 cells was inhibited obviously after treatment with dihydroartemisinin by the concentration of 30-480 μmol/L (P<0.05). The result of flow cytometry showed that dihydroartemisinin could block PANC-1 cell cycle in G2/M phase and induce cells apoptosis (P<0.05). The result of Western blotting showed that the expressions of Cdk1 and cyclin B1 were decreased and the expression of P21 increased after treatment with dihydroartemisinin. The expression of Bcl-2 was downregulated, expression of Bax was up-regulated, the ration of Bax/Bcl-2 was increased and the expression of cleaved Caspase-3, cleaved Caspase-9 and Cyto C were up-regulated. Conclusion Dihydroartemisinin can inhibit the proliferation of PANC-1 cells and induce apoptosis. The possible mechanism might be related to mitochondrial pathway.

Key words: Dihydroartemisinin, Pancreatic cancer, G2/M block, Western blotting, Human