PA-MSHA Inhibits Proliferation and Induces Apoptosis Through the Up-Regulation and Activation of Caspases in the Human Breast Cancer Cell Lines
PA-MSHA Inhibits Proliferation and Induces Apoptosis Through the Up-Regulation and Activation of Caspases in the Human Breast Cancer Cell Lines
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DOI：
10.1002/jcb.22241
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发表时间：
2009-09-01
影响因子：
4
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Liu, Zhe-Bin;Hou, Yi-Feng;Shao, Zhi-Ming
研究铜绿假单胞菌-人鼻敏感血凝素（PA-MSHA）对乳腺癌细胞株的增殖抑制作用，并探讨其作用机制。MCF-10A、MCF-7、MDA-MB-468和MDA-MB-231 HM细胞用PA-MSHA或PA（热灭活铜绿假单胞菌）以不同浓度和不同时间处理。透射电镜观察细胞超微结构的变化。流式细胞术（FCM）检测PA-MSHA诱导的细胞周期分布和凋亡，PI染色、ANNEXIN V-FITC染色和Hoechst 33258染色在荧光显微镜下观察PA-MSHA诱导的细胞凋亡。Western blot检测细胞凋亡相关分子的表达水平。在MDA-MB-468和MDA-MB-231 HM细胞中观察到PA-MSHA的时间依赖性和浓度依赖性细胞毒性作用，但在MCF-10A或MCF-7细胞中未观察到。PA-MSHA的出现改变了细胞形态，也就是说，自噬体增加，并且还可以观察到细胞质中的空泡。流式细胞仪PI染色、ANNEXIN V-FITC和Hoechst 33258染色显示，不同浓度的PA-MSHA均可诱导乳腺癌细胞凋亡，并使细胞周期阻滞于G（0）-G（1）期。切割型caspase 3、8、9和Fas蛋白表达水平与乳腺癌细胞凋亡的增加密切相关。与PA-MSHA浓度增加有直接关系，但与PA无直接关系。与PA完全不同，PA-MSHA可能通过诱导至少一条死亡受体相关的细胞凋亡信号通路介导的细胞凋亡，并影响细胞周期调控机制，从而对乳腺癌细胞产生抗增殖作用。J.细胞。108：195-206，2009. (C)2009 Wiley-Liss，Inc.
To investigate the effects of PA-MSHA (Pseudomonas aeruginosa-man nose sensitive hemagglutinin) on inhibiting proliferation of breast cancer cell lines and to explore its mechanisms of action in human breast cancer cells. MCF-10A, MCF-7, MDA-MB-468, and MDA-MB-231HM cells were treated with PA-MSHA or PA (Heat-killed P. aeruginosa) at different concentrations and different times. Changes of cell super-microstructure were observed by transmission electron microscopy. Cell cycle distribution and apoptosis induced by PA-MSHA were measured by flow cytometry (FCM) with PI staining, ANNEXIN V-FITC staining and Hoechst33258 staining under fluorescence microscopy. Western blot was used to evaluate the expression level of apoptosis-related molecules. A time-dependent and concentration-dependent cytotoxic effect of PA-MSHA was observed in MDA-MB-468 and MDA-MB-231HM cells but not in MCF-10A or MCF-7 cells. The advent of PA-MSHA changed cell morphology, that is to say, increases in autophagosomes, and vacuoles in the cytoplasm could also be observed. FCM with PI staining, ANNEXIN V-FITC and Hoechst33258 staining showed that the different concentrations of PA-MSHA could all induce the apoptosis and G(0)-G(1) cell cycle arrest of breast cancer cells. Cleaved caspase 3, 8, 9, and Fas protein expression levels were strongly associated with an increase in apoptosis of the breast cancer cells. There was a direct relationship with increased concentrations of PA-MSHA but not of PA. Completely different from PA, PA-MSHA may impart antiproliferative effects against breast cancer cells by inducing apoptosis mediated by at least a death receptor-related cell apoptosis signal pathway, and affecting the cell cycle regulation machinery. J. Cell. Biochem. 108: 195-206, 2009. (C) 2009 Wiley-Liss, Inc.