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中国临床药理学与治疗学 ›› 2015, Vol. 20 ›› Issue (6): 616-620.

• 基础研究 • 上一篇    下一篇

白杨素衍生物dFMAChR体外抗乳腺癌作用及其可能机制

王娟1,秦勇1,唐艳艳2,张敏2,覃丽3,张海涛3   

  1. 1. 南华大学附属第二医院药剂科
    2. 南华大学生命科学研究中心
    3. 南华大学药物药理研究所
  • 收稿日期:2014-11-10 修回日期:2014-12-09 出版日期:2015-06-26 发布日期:2015-06-29
  • 通讯作者: 张海涛 E-mail:hellozht@qq.com
  • 基金资助:

    湖南省教育厅科学研究项目

The Antitumor Effect and Potential Mechanism of dFMAChR in Human breast cancer in vitro

  • Received:2014-11-10 Revised:2014-12-09 Online:2015-06-26 Published:2015-06-29
  • Contact: Hai-Tao ZHANG E-mail:hellozht@qq.com

摘要: 目的 研究白杨素衍生物6,8-二-三氟甲基-5-羟基-7-乙酰氧基白杨素(dFMAChR)对体外培养人乳腺癌MCF-7细胞增殖和凋亡的影响,并对其体外抗乳腺癌作用机制进行初步探讨。方法 MTT法测定dFMAChR对MCF-7细胞增殖活性的影响;Hochest染色观察dFMAChR诱导MCF-7细胞凋亡的形态学改变;进一步DNA凝胶电泳证实dFMAChR确有诱导MCF-7细胞凋亡作用;Western Blot检测凋亡相关蛋白PPARγ、PTEN、p-Akt、Caspase-3的表达水平。结果 dFMAChR可剂量依赖性抑制人乳腺癌细胞的增殖,IC50值为8.51μM;3.0,10.0,30.0 μM dFMAChR处理人乳腺癌细胞48 h后Hochest染色镜下可见核浓缩的凋亡细胞,10.0,30.0 μM dFMAChR处理人乳腺癌细胞48 h后DNA凝胶电泳显示“梯形”条带,说明dFMAChR可诱导人乳腺癌MCF-7细胞凋亡;Western blot结果表明不同浓度的dFMAChR可浓度依赖性上调PPARγ、PTEN、 Caspase-3蛋白表达,下调p-Akt的表达。结论 dFMAChR具有体外抗乳腺癌作用,其诱导凋亡机制与激活PPARγ/PTEN信号通路,最终增加Caspase-3蛋白表达有关。

Abstract: 【Abstract】Objective To investigate the antitumor effect and potential mechanism of 6,8-ditrifluoromethy-5-hydroxyl-7-acetoy chrysin(dFMAChR) on human breast cancer MCF-7 cells. Methods Using MTT assay to assess the proliferative inhibitory effect of dFMAChR on MCF-7 cells; Hochest staining was used to observe the morphologic changes of apoptosis induced by dFMAChR in MCF-7 cells. DNA agarose electrophoresis was used to detect the fragment of DNA in MCF-7 cells. The protein level and activity of PPARγ、PTEN、p-Akt、Caspase-3 were tested by Western blot to explore the molecular mechanism of dFMAChR against breast cancer. Results dFMAChR inhibited proliferation of MCF-7 cells in a dose-dependent manner , the IC50 value of which was 8.51 μM; Hochest staining shown lots of apoptosis cells with nucleus condensation after treatment with dFMAChR(3.0, 10.0, 30.0 μM)for 48 h and DNA ladder bands could appear by DNA agarose gel electrophoresis after treatment with dFMAChR(10.0, 30.0 μM)for 48 h. It indicated that dFMAChR could significantly induce apoptosis of MCF-7 cells. The results of Western blot shown the expression of PPARγ、PTEN and Caspase-3 was enhanced while the expression of p-Akt was decreased in a concentration-dependent manner with treatment at various concentration dFMAChR for 48 h in MCF-7 cells. Conclusion dFMAChR had anti-breast cancer activity in vitro and its mechanism may be related to the activation of PPARγ/PTEN pathway and finally increased the expression of Caspase-3 and induced the apoptosis of MCF-7 cells .