BMP9 inhibits the growth of breast cancer cells by downregulation of the PI3K/Akt signaling pathway.
Li S1, Dai H2, He Y2, Peng S2, Zhu T2, Wu Y2, Li C3, Wang K2.
Author information
1Clinical Laboratory, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China.2Clinical Laboratory, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China.3Yubei District People’s Hospital of Chongqing, Chongqing 401120, P.R. China.
Abstract
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 cm3) was significantly lower compared with that of the MDA‑MB‑231/GFP (1.10±0.05 cm3) and MDA‑MB‑231 (1.12±0.12 cm3) 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.