title: Adenovirus mediated knockdown of bone morphogenetic protein 2 inhibits human lung cancer growth and invasion in vitro and in vivo.
abstract: Bone morphogenetic protein 2 (BMP-2) is a member of the TGF-beta 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 p85alpha (PI3Kp85alpha) 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 PI3Kp85alpha, 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 PI3K/AKT signaling pathway, and BMP-2 may be a potential therapeutic target for lung cancer.
authors.affiliation: Shanghai Chest Hospital, Shanghai, China.
authors.forename: X-Y
authors.initials: XY
authors.lastname: Ye
authors.forename: X-M
authors.initials: XM
authors.lastname: Niu
authors.forename: N-W
authors.initials: NW
authors.lastname: Tang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Xu
authors.forename: Z-M
authors.initials: ZM
authors.lastname: Li
authors.forename: Y-F
authors.initials: YF
authors.lastname: Yu
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.forename: S-W
authors.initials: SW
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000032:analysis / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D055396:Bone Morphogenetic Protein 2; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9