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