Nutlin-3和紫杉醇抑制乳腺癌MCF-7细胞株增殖和促进其细胞凋亡的作用和分子机制  

The functions and possible mechanism of Nutlin-3 and Taxol induced breast cancer cell MCF-7 apoptosis and proliferation inhibiton

作　　者：杜宁[1] 王猛 张云锋[1] 孙欣[1] 任宏[1] 刘大鹏[1] 

机构地区：[1]西安交通大学第一附属医院胸外2科,陕西西安710061

出　　处：《现代肿瘤医学》2017年第24期3934-3937,共4页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:81272418)

摘　　要：目的:研究Nutlin-3(N-3)与紫杉醇(Taxol,TAX)在抑制乳腺癌MCF-7细胞株增殖及促凋亡中的作用及分子机制。方法:使用N-3及TAX处理乳腺癌MCF-7细胞,研究二者对细胞增殖、细胞凋亡及细胞周期的影响,使用cyclin D1过表达的MCF-7细胞系(TRE3G-cyclin D1-MCF-7)研究N-3在TAX诱导的细胞凋亡及细胞增殖抑制中的作用及可能的机制。结果:N-3和TAX均能够上调乳腺癌MCF-7细胞中p53蛋白的表达,同时抑制cyclin D1蛋白的表达,从而有效地抑制乳腺癌MCF-7细胞的增殖,促进细胞凋亡,导致细胞周期发生G_0/G_1期阻滞,S期比例下降。N-3与TAX的联用可增敏TAX的抗肿瘤效果;在TRE3G-cyclin D1-MCF-7细胞中,过表达的cyclin D1可以抑制TAX对p53的上调,从而拮抗TAX对乳腺癌MCF-7细胞的促凋亡效应及增殖抑制效应,而N-3的应用可以重新上调p53的表达,有效逆转因过表达cyclin D1而导致的TAX对乳腺癌MCF-7细胞促凋亡效应及增殖抑制效应的拮抗作用,使得TRE3G-cyclin D1-MCF-7细胞再次对TAX治疗敏感。结论:N-3及TAX可能通过调节p53及cyclin D1的表达发挥抑制乳腺癌MCF-7细胞增殖并诱导其凋亡的效应。Objective ： To explore the functions and possible mechanism of Nutlin - 3 （ N - 3 ） and Taxol （TAX） induced breast cancer cell MCF - 7 apoptosis and proliferation inhibiton. Methods ： We detected the influence to cell proliferation, cell apoptosis and cell cycle in breast cancer cell MCF- 7 treated with Nutlin -3 （N -3 ） and TAX. In cyclin D1 overexpressed MCF - 7 ceils （ TRE3G - cyclin D1 - MCF - 7 ） , we explored the functions and possible mechanism of Nutlin -3 on affecting the TAX induced cancer cells apoptosis and proliferation inhibiton. Results：N - 3 and TAX can upregulate the expression of p53 in MCF - 7 cells. The upregulation of p53 and the downregulation of cyclin D1 caused by Nutlin- 3 and TAX could inhibite cell proliferation and increase cell apoptosis in breast cancer cell MCF -7, which could also block cell cycle in G0/G1 stage and reduce the proportion of S stage ceils. N -3 can enhance anti -tumor effect of TAX when associated use them. In TRE3G- cyclin D1 -MCF -7 cells, overexprcssion of cyclin D1 could inhibite the upregulation of p53 caused by TAX which can induce cell apoptosis and reduce cell proliferation. N -3 can restore upregulationg of p53 expression in TRE3G -cyclin D1 -MCF -7, which could reverse cyclin D1 overexpression inhibiting effect to TAX induced cell apoptosis and reduce cell proliferation. Conclusion： Possiblely through regulating the expression of p53 and cyclin DI, N -3 and TAX can induce cell apoptosis and pro- liferation inhibition in breast cancer cell MCF -7.

关 键 词：乳腺癌 p53 CYCLIN D1 Nutlin-3 紫杉醇 细胞凋亡 细胞周期 

分 类 号：R737.9[医药卫生—肿瘤]