阿法替尼对人乳腺癌细胞增殖与凋亡的影响及机制研究

发布时间：2018-02-21 19:02

本文关键词： 乳腺癌阿法替尼细胞周期细胞凋亡　出处：《中国肿瘤临床》2017年15期 　论文类型：期刊论文

【摘要】：目的:探讨酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)阿法替尼(afatinib)对乳腺癌细胞增殖、周期及凋亡的影响,并就阿法替尼与吉非替尼(gefitinib)对乳腺癌细胞的作用进行比较。方法:应用MTT法检测人乳腺癌细胞系MCF-7、T47D、MDAMB-231细胞活性,流式细胞术的PI染色法检测细胞周期变化以及Annexin-V/PI双染法检测细胞凋亡,通过Western blot法检测蛋白表达情况。结果:阿法替尼对MCF-7、T47D、MDA-MB-231细胞均有明显的抑制作用,IC_(50)分别为0.101、0.141、0.887μmol/L。阿法替尼对T47D、MDA-MB-231细胞作用24 h后G_0/G_1期细胞比例明显升高,细胞凋亡率增加,晚期的凋亡率分别为88.9%、58.1%,并可促进细胞凋亡通路蛋白PARP、caspase-3发生剪切。阿法替尼、吉非替尼使MDA-MB-231细胞的EGFR磷酸化水平受到明显抑制,相同浓度下,阿法替尼作用较吉非替尼更强、持续时间更长。结论:阿法替尼可显著抑制乳腺癌细胞增殖、促进其凋亡,且具有明显的量效关系,较吉非替尼具有更有效的作用。
[Abstract]:Aim: to investigate the effects of tyrosine kinase inhibitor (TKI), a tyrosine kinase inhibitor, on proliferation, cell cycle and apoptosis of breast cancer cells. The effects of afatinib and gefitinib on breast cancer cells were compared. Methods: MTT assay was used to detect the activity of human breast cancer cell line MCF-7T47DnMB-231. Flow cytometry was used to detect cell cycle change and Annexin-V/PI double staining method was used to detect cell apoptosis. Western blot assay was used to detect the protein expression. Results: Afatinib significantly inhibited MDA-MB-231 cell line MCF-7T47DN-MDA-MB-231. The number of Afatinib on T47DN-MDA-MB-231 cells was significantly higher than that of MDA-MB-231 cell line, and the cell apoptosis rate was increased after 24 hours of treatment with Afatinib (0.101) 0.141 ~ 0.141 渭 mol 路L ~ (-1) 路L ~ (-1). The late apoptotic rates were 88.9% and 58.1%, respectively, and the apoptotic pathway proteins PARP- caspase-3 were shearing. Afatinib and gefitinib significantly inhibited the phosphorylation of EGFR in MDA-MB-231 cells. At the same concentration, the effects of afatinib were stronger than that of gifetini. Conclusion: Afatinib can significantly inhibit the proliferation and promote the apoptosis of breast cancer cells, and has a significant dose-effect relationship, which is more effective than gefitinib.
【作者单位】：天津医科大学肿瘤医院乳腺一科国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心乳腺癌防治教育部重点实验室;
【基金】：国家自然科学基金面上项目(编号:81372843)资助~~
【分类号】：R737.9

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