›› 2019, Vol. 39 ›› Issue (11): 1561-1567.

• 研究论文 • 上一篇    下一篇

优降宁与奥沙利铂协同抑制乳腺癌细胞系MDA-MB-231增殖

汪湘1,杨凡2,刘钰妮1,王世恩1,夏燕3,曹春雨1   

  1. 1. 三峡大学医学院
    2. 宜昌市第二人民医院(三峡大学第二人民医院)
    3. 湖北民族学院附属民大医院
  • 收稿日期:2018-11-01 修回日期:2019-05-07 出版日期:2019-11-05 发布日期:2019-11-05
  • 通讯作者: 曹春雨 E-mail:caocy@ctgu.edu.cn
  • 基金资助:
    以HDAC5-LSD1基因表达调控轴为靶点的抗三阴性乳腺癌实;联合抑制HDAC/LSD1用于抗三阴性乳腺癌的实验研究;Notch为靶点的抗类风湿关节炎实验研究

Pargyline and oxaliplatin synergistically inhibits proliferation of breast cancer cell line MDA-MB-231

  • Received:2018-11-01 Revised:2019-05-07 Online:2019-11-05 Published:2019-11-05
  • Contact: Chun-Yu CAO E-mail:caocy@ctgu.edu.cn

摘要: 目的 研究优降宁抑制赖氨酸特异性去甲基化酶1(LSD1)对奥沙利铂抗人三阴性乳腺癌MDA-MB-231细胞增殖作用的影响及其用于抗人三阴性乳腺癌临床研究的潜在价值。方法 优降宁和奥沙利铂单独以及联合处理MDA-MB-231细胞后,CCK-8法分析细胞增殖。Western blot检测细胞内LSD1表达及其下游底物组蛋白H3K4二甲基化修饰水平、下游基因E-cardherin表达和Bax、Bcl-2及细胞浆内细胞色素C蛋白水平。annexinV/PI双染法检测细胞凋亡。结果 优降宁能够时间和剂量依赖性地抑制MDA-MB-231细胞增殖(P﹤0.05)。1 mmol/L优降宁可显著抑制MDA-MB-231细胞内LSD1蛋白的组蛋白去甲基化酶活性(P﹤0.05)。1 mmol/L优降宁和奥沙利铂联合处理具有抑制MDA-MB-231细胞增殖的药物协同效应。1 mmol/L优降宁显著促进奥沙利铂诱导MDA-MB-231细胞凋亡发生(P﹤0.05),伴随着Bax基因表达上调、Bcl-2基因表达下调和细胞色素C从线粒体向细胞浆的转移。过表达LSD1则可部分逆转优降宁与奥沙利铂对MDA-MB-231细胞增殖的协同抑制(P﹤0.05)。结论 优降宁通过抑制LSD1促进奥沙利铂诱导的MDA-MB-231细胞增殖抑制、细胞凋亡,并产生药物协同效应抑制MDA-MB-231细胞增殖。

关键词: 赖氨酸特异性去甲基化酶-1, 优降宁, 奥沙利铂, 三阴性乳腺癌, MDA-MB-231细胞

Abstract: Objective: To study the effect of combine treatment of LSD1 inhibitor pargyline and oxaliplatin on the proliferation of MDA-MB-231 cells and to evaluate the potential value of oxaliplatin combined with pargyline in the treatment of human triple negative breast cancer. Methods: CCK-8 method was used to analyze the effects of LSD1 inhibitor pargyline alone or combine with oxaliplatin on cell growth. Histone H3K4me2 methylation modification and protein expression of Bcl-2, Bax, cytochrome C, E-cardherin and LSD1 was detected with Western blotting. Apoptosis was analyzed with annexin V/PI double staining. Results: Pargyline could significantly inhibit MDA-MB-231 cells growth in a time and dose dependent manner. 1 mmol/L pargyline dramatically inhibited demethylase activity of LSD1 on histone H3K4me2 in MDA-MB-231 cells, meanwhile protein expression of LSD1 was not disturbed in 1 mmol/L pargyline treated MDA-MB-231 cells. Pargyline combined with oxaliplatin displayed a synergistic inhibitory effect on MDA-MB-231 cells growth. Oxaliplatin alone could induce apoptosis in MDA-MB-231 cells which was identified with increased protein expression of Bax, down-regulated protein expression of Bcl-2 and the translocation of cytochrome C from mitochondria to cytoplasm. Furthermore, 1 mmol/L pargyline alone could not induce apoptosis, but significantly pormoted oxaliplatin-induced MDA-MB-231 cells apoptosis. LSD1 over-expression partially reversed the promoting role of pargylineon oxaliplatin-mediated MDA-MB-231 cells proliferation inhibition. Conclusions: Combination of pargyline and oxaliplatin synergistically inhibits MDA-MB-231 cells proliferation, and pargyline promotes oxaliplatin-induced apoptosis and proliferation by inhibiting LSD1.

Key words: LSD1, Pargyline, Oxaliplatin, triple negative breast cancer, MDA-MB-231 cells

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