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姚轶敏.川楝素上调FOXO1的表达增强多柔比星的体外抗乳腺癌活性[J].浙江中西医结合杂志,2018,28(2):
川楝素上调FOXO1的表达增强多柔比星的体外抗乳腺癌活性
toosendanin enhances the anti-tumor effect of doxorubicin on breast cancer in vitro by upregulating the expression of FOXO1
投稿时间:2017-09-28  修订日期:2017-11-24
DOI:
中文关键词:  川楝素  多柔比星  乳腺癌  FOXO1  凋亡
英文关键词:toosendanin  doxorubicin  breast cancer  FOXO1  apoptosis
基金项目:
作者单位E-mail
姚轶敏* 浙江中医药大学附属第一医院 myonlylovexujing@163.com 
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中文摘要:
      目的: 探讨川楝素对乳腺癌多柔比星化疗的辅助治疗作用并研究其机制。方法: MTT法检测乳腺癌细胞系MDA-MB-435和MDA-MB-231的细胞活力;流式细胞术检测MDA-MB-435的细胞凋亡;western blot实验检测MDA-MB-435细胞中FOXO1、Bim、Noxa的表达水平,细胞色素c的释放水平及caspase-9、caspase-3的活化水平。结果: 川楝素明显增强MDA-MB-435和MDA-MB-231细胞系对不同浓度多柔比星的敏感性。多柔比星联合川楝素处理的MDA-MB-435的相对细胞活力(0.55±0.04)显著低于多柔比星单治疗组(0.87±0.07,P<0.05)和多柔比星+川楝素+FOXO1 siRNA组(0.79±0.07,P<0.05)。多柔比星联合川楝素处理的MDA-MB-435的细胞凋亡率(34.2±2.8)显著高于多柔比星单治疗组(9.3±0.8,P<0.05)和多柔比星+川楝素+FOXO1 siRNA组(12.5±1.1,P<0.05)。多柔比星联合川楝素处理的MDA-MB-435细胞中FOXO1、Bim、Noxa的表达水平,细胞色素c的释放水平及caspase-9、caspase-3的活化水平均显著高于多柔比星单治疗组和多柔比星+川楝素+FOXO1 siRNA组。结论: 川楝素上调FOXO1的表达增强多柔比星的体外抗乳腺癌活性。
英文摘要:
      AIM: To investigate the adjuvant effect and mechanism of toosendanin on enhancing the anti-tumor effect of doxorubicin against breast cancer. Methods: MTT assay was performed to measure the cell viability of MDA-MB-435 and MDA-MB-231. Flow cytometry analysis was performed to detect the cell apoptosis of MDA-MB-435. Western blot analysis was performed to evaluate the expression of FOXO1, Bim, Noxa, and release of cytochrome c, and the activation of caspase-9 and caspase-3 in MDA-MB-435 cells. Results: Toosendanin significantly increased the sensitivity of MDA-MB-435 and MDA-MB-231 cell lines to different concentrations of doxorubicin. Relative cell viability of MDA-MB-435 co-treated with doxorubicin and toosendanin (0.55±0.04) was significantly lower than the doxorubicin single treatment group (0.87±0.07, P<0.05) and the doxorubicin + toosendanin + FOXO1 siRNA group (0.79±0.7, P<0.05). Apoptotic rate (34.2±2.8) of MDA-MB-435 co-treated with doxorubicin and toosendanin was significantly higher than the doxorubicin single treatment group (9.3±0.8, P<0.05) and doxorubicin + toosendanin + FOXO1 siRNA group (12.5±1.1, P<0.05). Expression of FOXO1, Bim, Noxa, and release of cytochrome c, and activation of caspase-9 and caspase-3 in MDA-MB-435 cells co-treated with doxorubicin and toosendanin was significantly increased than the doxorubicin single treatment group and doxorubicin + toosendanin + FOXO1 siRNA group. Conclusion: Toosendanin enhances the anti-tumor effect of doxorubicin on breast cancer in vitro by upregulating the expression of FOXO1.
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