PIB5PA增强三阴性乳腺癌MDA-MB-231细胞对紫杉醇的敏感性的研究  

PIB5PA enhance the Sensitivity of Triple-negative Breast Cancer Cell line MDA-MB-231 to Paclitaxel through Up-regulation of Bim

作　　者：张楠楠[1] 胡春松[2] 陈振东[3] 

机构地区：[1]安徽省阜阳市人民医院,安徽阜阳236006 [2]安徽医科大学基础医学院,安徽合肥230032 [3]安徽医科大学第二附属医院,安徽合肥230022

出　　处：《时珍国医国药》2016年第1期255-256,F0003,F0004,共4页Lishizhen Medicine and Materia Medica Research

基　　金：安徽省自然科学基金(No.1208085MH134)

摘　　要：目的探讨PIB5PA(phosphatidylinositol 4,5-bisphosphate5-phosphatase)基因转染人三阴性乳腺癌MDA-MB-231细胞后对紫杉醇敏感性的影响。方法体外培养人乳腺癌MCF-7和MDA-MB-231细胞株,MTT法观察不同浓度(0,0.1,0.2,0.3,0.4,0.5μmol/L)紫杉醇处理后对两株细胞生存率的影响;流式细胞PI单染法检测两株细胞凋亡率的差异;蛋白免疫印迹法检测0.3μmol/L紫杉醇处理两株细胞不同时间点Bcl-2家族成员蛋白表达差异。将p CGNPIB5PA质粒转染对紫杉醇相对不敏感MDA-MB-231细胞,0.3μmol/L紫杉醇处理24h,免疫蛋白印迹法检测PIB5PA,磷酸化Akt以及Bcl-2家族成员蛋白的表达,MTT和PI单染法检测MDA-MB-231细胞对紫杉醇敏感性的改变。结果MDA-MB-231细胞对紫杉醇敏感性较差,过表达PIB5PA后细胞生存率明显降低,细胞中磷酸化Akt水平降低,Bim(Bcl-2 interacting mediator of cell death)表达明显增高,对紫杉醇敏感性明显增强。结论 PIB5PA可能通过上调Bim表达增强三阴性乳腺癌MDA-MB-231细胞对紫杉醇的敏感性。Objective To investigate the role of PIB5 PA in enhancing sensitivity of triple- negative breast cancer cell line MDA- MB- 231 to Paclitaxel. Methods Breast cancer cell lines MCF- 7 and MDA- MB- 231 was treated with different concentrations（ 0,0. 1,0. 2,0. 3,0. 4,0. 5μmol/L） of Paclitaxel,Then MTT and flow cytometry propidium iodide（ PI） staining assay was used to measure these two cell lines survivai and apoptosis respectiveiy; Westem Blotting was applied toobserve the Bcl- 2 family expression at different time points after treated with0. 3μmol/L Paclitaxel. MDA- MB- 231,which was less sensitive to Paclitaxel relatively,was transfected with p CGN- PIB5 PA plasmids,followed by treatmen 0. 3μmol/L Paclitaxel for 24 hours. Then the expression of PIB5 PA Phosphorvlated AKt and Bcl- 2 family was detected.. Results After the overexpression of PIB5 PA,the sensitivity of MDA- MB- 231 to Paclitaxel was significantly increased comparison with that transfected with control plasmids,showing the reduced cell survival and increased cell apoptosis. The Bim expression was up- regulated and Phosphorvlated AKt was decreased. Conclusion PIB5 PA could enhance sensitivity to Paclitaxel Probably by promoting the Bim expression in triple- negative breast cancer cell line MDA- MB- 231.

关 键 词：紫杉醇 乳腺癌 PIB5PA 凋亡 BIM 

分 类 号：R285.5[医药卫生—中药学]