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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 whether BMP9 can inhibit the growth of human breast cancer cells MDA-MB-231 through other non-classical BMPs / SMAD signaling pathway. In this study, immunohistochemistry was used to detect the expression of BMP9, Akt and Akt phosphorylation proteins in clinical breast cancer tissues and paracancerous tissues. Western blot was used to detect the expression of BMP9 or targeted BMP9 in breast cancer cells PI3K / Akt signaling pathway Akt protein and Akt phosphorylation protein expression in nude mice xenograft animal model confirmed that BMP9 can inhibit breast cancer growth, and its changes in cell proliferation of nuclear antigen PCNA expression. The results showed that the expression of BMP9 in cancerous tissues of patients with clinical breast cancer was significantly lower than that in adjacent tissues. The expression of BMP9 and the expression of Akt phosphorylation protein in cancerous tissues were significantly decreased. The expression of MDA-MB-231 / BMP9 group, the expression of Akt phosphorylation protein in MCF7 / si BMP9 group was significantly lower than that in MDA-MB-231 / GFP group and MCF7 / si BMP9 group The tumor size of MDA-MB-231 / BMP9 was significantly lower than that of MDA-MB-231 / GFP (3.102 ± 0.027) on the 21st day after tumorigenesis. The positive rate of PCNA in MB-231 / BMP9 was (26.3 ± 3.1)%, which was significantly lower than that in MDA-MB-231 / GFP (57.8 ± 5.3)%. It is concluded that BMP9 can inhibit the growth of breast cancer MDA-MB-231 cells by inhibiting PI3K / Akt signaling pathway to play a role.