The effect of bone morphogenetic protein-2 on epithelial-mesenchymal transition in lung cancer cells and its related mechanism / 肿瘤

ABSTRACT

Objective: To investigate the effect of bone morphogenetic protein-2 (BMP-2) on epithelial-mesenchymal transition (EMT) of lung cancer cells and its possible molecular mechanism. Methods: Human lung adenocarcinoma cancer A549 cells were treated with different concentrations of BMP-2 (10, 50 and 100 μg/mL) for 24 h. The protein expression levels of EMT markers including E-cadherin (E-cad), vimentin and matrix metalloproteinase-2 (MMP-2) were detected by immunohistochemistry and Western blotting. The migration and invasion capacities of A549 cells were examined by wound healing and Matrigel invasion assays. The apoptosis was analyzed by cytometry flow (FCM). The EMT, migration and invasion capabilities and the apoptosis of A549 cells treated with p38 mitogen-activated protein kinase (p38 MAPK)-specific inhibitor SB203580 combined with 100 μg/mL BMP-2 were detected. Results: BMP-2 could reduce E-cad expression and increase vimentin and MMP-2 protein expressions in A549 cells in a concentration-dependent manner. The wound healing rate of the intervention group (100 μg/mL BMP-2) was significantly higher than that of the blank control group (P < 0.05). The number of the cells penetrating the membrane was increased significantly (P < 0.05), and the early apoptosis rate of A549 cells was decreased through 100 μ g/mL BMP-2 stimulation (P < 0.05). p38MAPK pathway-specific inhibitor SB203580 could partially decrease the expression of E-cad (P = 0.039) and increase the expressions of vimentin and MMP-2 (P = 0.023, P = 0.040). As compared with the cells treated with BMP-2 alone, the combination of BMP-2 and SB203580 could decrease the wound healing rate of A549 cells (P = 0.029), the number of the cells pentrating the membrane was reduced (P = 0.009), and the early apoptosis rate of the cells was increased (P = 0.046). Conclusion: BMP-2 can promote the EMT of human lung adenocarcinoma cancer A549 cells in vitro, inhibit the early apoptosis, and increase the migration and invasion capacities of lung cancer cells. This process is associated with the activation of p38MAPK signaling pathway.