紫杉醇载药胶束对人肺癌A549细胞增殖与凋亡的影响  

Effects of paclitaxel loaded-drug micelles on cell proliferation and apoptosis of human lung cancer A549 cells

作　　者：王琳[1] 余瑞双 杨文亮[1] 栾淑娟[1] 秦本凯 庞晓斌[1] 杜冠华 

机构地区：[1]河南大学药物研究所,河南开封475004 [2]中国医学科学院、北京协和医学院药物研究所,国家药物筛选中心,北京100050

出　　处：《药学学报》2015年第10期1240-1245,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81273652,51375142)

摘　　要：本文研究了以聚乙二醇-聚己内酯共聚物为载体制备的紫杉醇载药胶束(m PEG-PCL-PTX)对人肺癌A549细胞增殖和凋亡的影响,探讨其抗肿瘤的可能机制。以体外培养的人肺癌A549细胞为研究对象,四甲基偶氮唑盐(MTT)法检测m PEG-PCL-PTX对细胞增殖的抑制作用;流式细胞仪检测细胞周期;Hoechst/PI染色检测细胞凋亡;RT-PCR检测A549细胞Bax、Bcl-2、Caspase-3 m RNA的表达;Western blot检测A549细胞Bax、Bcl-2蛋白表达。结果显示,空白聚合物胶束体外基本无毒性,m PEG-PCL-PTX对A549细胞增殖有明显抑制作用,并使细胞周期阻滞于G2/M期;载药胶束促进A549细胞凋亡,使A549细胞Bcl-2基因和蛋白表达下调,Bax表达上调,同时上调Caspase-3基因表达。结果表明,含腙键p H敏感聚合物体外基本无毒性,载药胶束m PEG-PCLPTX对人肺癌A549细胞的增殖有抑制作用,对A549细胞的凋亡有促进作用。This study was conducted to investigate the paclitaxel loaded by hydrazone bonds in poly（ethylene glycol）-poly（caprolactone） micelles （mPEG-PCL-PTX） on proliferation and apoptosis of human lung cancer A549 cells and its possible mechanisms of anti-tumor activity. The cell proliferation was measured with MTT assay. Flow cytometry were used to analyze the cell cycle. The cell apoptosis was analyzed using Hoechst/PI staining. The expression levels of apoptotic genes expression in the mitochondrial apoptosis pathway were detected by RT-PCR and Western blotting, respectively. The mPEG-PCL-PTX could inhibit the proliferation of A549 cells and promote the apoptosis. The Bax, caspase-3 protein expression were increased while Bcl-2 protein expression was decreased in A549 cells. Results showed that the polymer containing hydrazone bond is non-toxic in vitro, the mPEG-PCL-PTX micelles can inhibit the proliferation and induce the apoptosis ofA549 cells.

关 键 词：紫杉醇 胶束 肺癌A549细胞 增殖 细胞周期 凋亡 

分 类 号：R963[医药卫生—微生物与生化药学]