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BH3类似物对乳腺癌细胞的促凋亡作用 被引量:1

The Pro-apoptosis Efficacy of BH3Mimics in Breast Cancer Cells
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摘要 通过查找NCBI的Gene数据库,发现Bcl-2家族抗凋亡成员的mRNA在大部分乳腺癌细胞系中高表达.根据以往文献报道,Bcl-2家族抗凋亡成员的高表达能够促进肿瘤的生长.BH3类似物是一类针对Bcl-2家族抗凋亡成员的新型靶向抑制剂.据此,在7种乳腺癌细胞系中测试了3种BH3类似物对细胞增殖的影响.在两种细胞系中通过克隆形成实验和TUNEL实验研究了BH3类似物对单个肿瘤细胞增殖和细胞群体凋亡的影响.结果表明,ABT-737对大部分乳腺癌细胞系有明显的生长抑制作用;ABT-199对大部分乳腺癌细胞系有一定抑制作用;Tw-37对两种乳腺癌细胞系有较强抑制作用,这些抑制作用是通过细胞凋亡产生的.Bcl-2家族抗凋亡成员对于T47D和BT-549细胞系的存活不是非常重要.联合用药实验表明ABT-737在BT-549和T47D细胞系中可以增强阿霉素和紫杉醇的作用.综上所述,BH3类似物可以通过细胞凋亡的途径引起乳腺癌细胞的死亡,同时Bcl-2家族抗凋亡成员可能可以成为治疗乳腺癌的新靶点. NCBI's Gene Database shows that pro-survival members of Bcl-2 family always have a high expression in breast cancer cell lines. Previous studies have shown pro-survival members of Bcl-2 family would promote tumor progression. BH3 mimic is a new type of targeted inhibitor and could antagonize pro-survival members of Bcl-2 family. Therefore, we tested three BH3 mimic inhibitors whether they have killing effects on 7 breast cancer cell lines. We conduct clone formation and TUNEL assays in MDA-MB-231 and MCF-7 cell lines to evaluate single cell's proliferation and apoptosis of Bcl-2 family inhibitor treated tumor cells. Our results demonstrated ABT-737 had an obvious inhibitory effect in most breast cancer cell lines. ABT-199 has a mild efficacy in some breast cancer cell lines. Tw-37 has a strong efficacy in two breast cancer cell lines. This inhibitory effect is caused by apoptosis. Bcl-2 family did not play important role for the survival of BT-549 and T47D cells. Moreover, drug combination experiment indicated ABT-737 could enhance efficacy of doxorubicin and paclitaxel. Above all, the results show BH3 mimics could cause cell apopotosis in breast cancer cells, and pro-survival members of Bcl-2 family would be potential drug target in treating breast cancer.
出处 《复旦学报(自然科学版)》 CAS CSCD 北大核心 2015年第1期8-15,F0002,共9页 Journal of Fudan University:Natural Science
基金 国家自然科学基金面上项目(81372346)
关键词 乳腺癌 Bcl-2家族抗凋亡成员 细胞凋亡 BH3类似物 靶向治疗 breast cancer pro-survival members of Bcl-2 family cell apoptosis BH3 mimics targeting therapy
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参考文献9

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同被引文献12

  • 1徐咏梅,杨国旺,王笑民,韩冬,于洁,赵文硕.丹栀逍遥散加减治疗乳腺癌内分泌综合征65例临床观察[J].河北中医,2005,27(9):676-676. 被引量:19
  • 2汤睿,朱正纲.凋亡途径与肿瘤治疗[J].世界华人消化杂志,2005,13(20):2469-2472. 被引量:27
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  • 9何立丽,孙桂芝.孙桂芝治疗乳腺癌经验[J].北京中医药,2009,28(1):18-19. 被引量:21
  • 10齐殿君,刘冰,张清富,冯亮.BALB/C小鼠MCF-7和MDA-MB-231乳腺癌移植模型的建立和评价[J].中国慢性病预防与控制,2014,22(1):84-85. 被引量:6

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