The first two authors contributed equally to this work Bone morphogenetic protein 2 (BMP-2) is a member of the TGF-IJ superfamily of signaling molecules, and has been shown to function as a tumor suppressor involved in development and progression of many malignancies. BMP-2 has previously been reported to be closely correlated with lung cancer. But, the role and molecular mechanisms of BMP-2 in lung cancer have not yet been comprehensively explained. The present study aims to elucidate the role of BMP-2 in growth and invasion of human lung adenocarcinoma (LAC) in vitro and in vivo. Adenovirus vector-mediated BMP-2 small hairpin RNA (shBMP-2) was used to transfect into A549 LAC cells to determine the functional relevance of BMP-2 and tumor growth and invasion in vitro and in vivo, and further investigate the expression levels of BMP-2, vascular endothelial growth factor (VEGF), matrix metallopeptidase-9 (MMP-9), phosphatidylinositol 3-kinase p85a (PI3Kp85a) and phosphorylated AKT (P-AKT). As a result, LAC cell proliferation and invasion were significantly diminished by knockdown of BMP-2 indicated by MTT and Transwell assays, and cell apoptosis and cycle arrest were markedly induced indicated by flow cytometry. When BMP-2 expression was knocked down, the expression of PI3Kp85a, p-AKT, VEGF and MMP-9 was also down-regulated in LAC cells. In addition, the tumor volumes in LAC subcutaneous nude mouse model treated with shBMP-2 were significantly smaller than those in control and ad-GFP groups. Taken together, our findings indicate that knockdown of BMP-2 inhibits growth and invasion of LAC cells possibly via blockade of the PI3KJ AKT signaling pathway, and BMP-2 may be a potential therapeutic target for lung cancer.Lung cancer was the most commonly diagnosed cancer as well as the leading cause of cancer death in males in 2008 globally. Among females, it was the fourth most commonly diagnosed cancer and the second leading cause of cancer death (1). The current best approach for treatment of cancer is complete surgical removal of the tumor with the adjacent lymph nodes. However, the efficacy of this therapeutic approach, as well as hormone-, radio-, and chemo-therapy, is very limited (2). Tumor is also a genetic disease developing from a multi-step process. Single or multiple gene mutations is related to growth control, invasion and metastasis form the molecular genetic basis of malignant transformation and tumor progression. Therefore, identification of key genes or targets related to tumorigenesis is
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