BMP9/PI3K/Akt信号通路抑制乳腺癌MDA-MB-231细胞生长  

BMP9 Inhibit the Growth of MDA-MB-231 Breast Cancer Cells through PI3K/Akt Cell Signaling Pathway

作　　者：刘洋[1] 张银 朱天金[2] 唐治贵[2] 王科[2] 

机构地区：[1]重庆医科大学附属永川医院胃肠外科,重庆402160 [2]重庆医科大学附属永川医院检验科,重庆402160

出　　处：《基因组学与应用生物学》2016年第10期2539-2544,共6页Genomics and Applied Biology

基　　金：国家自然科学基金(30800658);重庆市教委课题(KJ1500202)基金共同资助

摘　　要：探讨骨形态发生蛋白9是否可通过其它非经典BMPs/SMAD信号通路来抑制人乳腺癌癌细胞MDA-MB-231的生长。本研究采用免疫组化方法检测临床乳腺癌患者癌组织和癌旁组织中BMP9、Akt总蛋白和Akt磷酸化蛋白表达,采用Western blot检测过表达BMP9或靶向干扰BMP9后,对乳腺癌细胞中PI3K/Akt信号通路中Akt总蛋白和Akt磷酸化蛋白表达的影响,通过裸鼠异位移植瘤动物模型证实BMP9可抑制乳腺癌生长,及其对细胞增殖核抗原PCNA表达改变。结果显示,临床乳腺癌患者癌组织中BMP9表达明显低于癌旁组织,癌组织中存在BMP9表达,Akt磷酸化蛋白表达明显降低;BMP9腺病毒感染MDA-MB-231后,MDA-MB-231/BMP9组的Akt磷酸化蛋白表达明显低于MDA-MB-231/GFP,干扰掉MCF7中内源性BMP9后,MCF7/si BMP9组Akt磷酸化蛋白表达明显高于MVF7/si NC组;裸鼠移植瘤动物模型在成瘤后的第21天,MDA-MB-231/BMP9瘤体大小为(0.329±0.047)明显小于MDA-MB-231/GFP(3.102±0.027),PCNA染色显示MDA-MB-231/BMP9的PCNA阳性率为(26.3±3.1)%,明显低于MDA-MB-231/GFP(57.8±5.3)%。由此得出结论,BMP9抑制乳腺癌MDA-MB-231细胞生长还可以通过抑制PI3K/Akt信号通路激活来发挥作用。To investigate the inhibitory effect of BMP9 on the growth of human breast cancer cells MDA-MB-231 through non-classical BMPs/SMAD signaling pathway. The expression of BMP9, Akt and p-Akt in clinical breast cancer tissues and paracancerous tissues were detected by immunohistochemical. The expression of Akt and p-Akt on PI3KJAkt signaling pathway were detected by the Western blot while over expression or interference BMP9 in breast cancer cells. The expression of PCNA in nude mice xenografl animal model was used to confirrm BMP9 can inhibit the proliferation of breast cancer. The results showed that expression of BMP9 was significantly lower in clinical breast cancer tissue than that the para cancer tissues. Once, BMP9 expression was increased, p-Akt expression was significantly decreased, the p-Akt expression ofMDA-MB-231/BMP9 was significantly lower than MDA-MB-231/GFP after BMP9 adenovirus infected MDA-MB-231and the p-Akt protein expression of MCF7/ siBMP9 was significantly higher than the MCF7/siNC after BMP9 interfere adenovirus infected MCF7. The tumor size ofMDA-MB-231/BMP9 （0.329±0.047） was significantly lower than MDA-MB-231/GFP （3.102±0.027） after tumor formation 21 days in nude mice transplanted tumor animal model, the PCNA-positive cell rate decreased from （57.8±5.3）% to （26.3±3.1）% by the PCNA immunohistochemical. It is concluded that BMP9 inhibits the gr- owth of breast cancer MDA-MB-231 cells through inhibiting the activation of PI3K/Akt signaling pathway.

关 键 词：骨形态发生蛋白9 乳腺癌 生长 PI3K/AKT信号通路 

分 类 号：R737.9[医药卫生—肿瘤]