BMP9 inhibits the growth of breast cancer cells by downregulation of the PI3K/Akt signaling pathway

Bone morphogenetic protein 9 (BMP9) is a member of the BMP family, which is involved in the regulation of tumor biogenesis, development and metastasis. The present study aimed to investigate whether BMP9 inhibits the growth of MDA-MB-231 breast cancer cells via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. It was shown that the expression level of BMP9 was significantly decreased, while that of phosphorylated Akt (p-Akt) was markedly increased in breast cancer tissues compared with these levels in the normal adjacent tissues. An adenovirus overexpressing BMP9 was used to infect the MDA-MB-231 cells. The expression level of p-Akt in the MDA-MB-231/BMP9 group was shown to be significantly lower than that in the MDA-MB-231/green fluorescent protein (GFP) and MDA-MB-231 control groups. The expression levels of cyclins D1, B1 and E1, c-Myc and matrix metalloproteinase 9 (MMP9) in the MDA-MB-231/BMP9 group were also reduced. The generation of a nude mouse xenograft tumor model revealed that the tumor volumes of the MDA-MB-231/BMP9 group (0.32 +/- 0.05 cm(3)) was significantly lower compared with that of the MDA-MB-231/GFP (1.10 +/- 0.05 cm(3)) and MDA-MB-231 (1.12 +/- 0.12 cm(3)) groups, and the expression level of p-Akt protein in the MDA-MB-231/BMP9 group was significantly lower compared with that of the MDA-MB-231/GFP and MDA-MB-231 groups in the nude mouse xenograft model. Taken together, these results indicate that BMP9 inhibits the growth of MDA-MB-231 breast cancer cells by inhibiting the PI3K/Akt signaling pathway both in vivo and in vitro.