中文摘要：

目的：研究骨形态发生蛋白-2（bonemorphogenetic protein-2，BMP-2）对肺癌细胞上皮-间质转化（epithelial-mesenchymal transition，EMT）的影响，并探讨其可能的分子作用机制。方法：用不同质量浓度的BMP-2（10、50和100μg／mL）处理人肺腺癌A549细胞24h，采用免疫组织化学法检测A549细胞中上皮细胞标志物E-钙黏蛋白（E-cadherin，E-cad）表达水平的变化，蛋白质印迹法检测A549细胞中E-cad、间质细胞标志物波形蛋白（vimentin）及基质金属蛋白酶-2（matrix metalloproteinases-2，MMP-2）表达的变化；分别采用划痕实验和Matrigel基质胶小室法检测对A549细胞迁移及侵袭能力的影响；FCM法检测细胞凋亡的变化。随后，通过p38丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路抑制剂SB203580联合BMP-2（100~g／mL）作用于A549细胞，检测p38MAPK信号通路阻断后对上述A549细胞EMT、迁移和侵袭能力及凋亡的影响。结果：BMP-2呈浓度依赖性降低A549细胞中E-cad蛋白的表达，并促进间质标志物vimentin蛋白及MMP-2蛋白表达的增加；A549细胞在BMP-2（100μg／mL）刺激下划痕愈合率明显高于空白对照组（P〈0．05），穿过小室膜的细胞数显著增多（P〈0．05），细胞的早期凋亡率降低（P〈0．05）。SB203580能部分抑制BMP-2诱导的A549细胞中E-cad表达的降低（P=0．039），以及vimentin和MMP-2蛋白表达的增高（P=0．023和P=0．040）；BMP-2联合SB203580作用下A549细胞划痕愈合率较BMP-2单药组降低（P=0．029），穿过小室滤膜的细胞数较BMP-2单药组明显减少（P=0．009），细胞的早期凋亡率较BMP-2单药组增加（P=0．046）。结论：BMP-2能够在体外促进肺腺癌A549细胞发生EMT，抑制细胞的早期凋亡，并促进细胞的迁移和侵袭，这一过程与p38MAPK信号通路的激活有关。

英文摘要：

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 aroup （P 〈 0.05）. The number of the cells nenetratina the membrane was increased significantly （P 〈 0.05）, and the early apoptosis rate of A549 cells was decreased through 100 μg/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 ofvimentin 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