目的: 探讨肝激酶B1(liver kinase B1, LKB1)基因对肺癌细胞增殖及迁移侵袭的影响及作用机制。方法: LKB1过表达慢病毒转染A549细胞,设立A549空白组(不转染慢病毒)、NC-A549组(转染空载体)、LKB1-A549组(转染LKB1基因)。Western blot和RT-qPCR检测细胞转染后LKB1的表达水平;CCK8实验检测LKB1过表达对A549细胞增殖的影响;Transwell实验分别检测LKB1过表达对A549细胞迁移、侵袭的影响;RT-qPCR检测LKB1过表达对上皮间质转化标志物表达的影响;Western blot检测LKB1过表达对血管内皮生长因子A(vascular endothelial growth factor A, VEGFA)及原肌球调节蛋白1(tropomodulin-1, TMOD1)表达的影响。结果: 与A549空白组相比,LKB1-A549组LKB1表达增高(P＜0.01),细胞增殖、迁移及侵袭能力均降低(P＜0.01),上皮间质转化标志物E-cadherin表达增高(P＜0.001),N-cadherin表达下降(P＜0.01),血管内皮生长因子A及原肌球调节蛋白1表达下降(P＜0.01)。结论: LKB1过表达抑制人肺癌A549细胞的增殖、迁移、侵袭、上皮间质转化及血管生成,可能成为肺癌治疗的潜在靶点。
Objective: To investigate the effect of liver kinase B1 ( LKB1 ) gene on the proliferation, migration and invasion of lung cancer cells and its mechanism. Methods: LKB1 overexpression lentivirus was transfected into A549 cells, and A549 blank group (without transfection of lentivirus), NC-A549 group (transfected with empty vector) and LKB1-A549 group (transfected with LKB1 gene) were established. Western blot and RT-qPCR were used to detect the expression level of LKB1 after transfection. CCK8 assay was used to detect the effect of LKB1 overexpression on the proliferation of A549 cells. Transwell assay was used to detect the effect of LKB1 overexpression on the migration and invasion of A549 cells. The effect of LKB1 overexpression on the expression of epithelial-mesenchymal transition markers was detected by RT-qPCR. The effects of LKB1 overexpression on the expression of vascular endothelial growth factor A and tropomyosin 1 were detected by Western blot. Results: Compared with the A549 blank group, the expression of LKB1 in the LKB1-A549 group was increased (P＜0.01), the cell proliferation, migration and invasion abilities were decreased (P＜0.01), the expression of epithelial-mesenchymal transition marker E-cadherin was increased (P＜0.01), and the expression of N-cadherin was decreased (P＜0.01). The expression of vascular endothelial growth factor A (VEGFA) and tropomodulin-1 (TMOD1) decreased (P＜0.01). Conclusion: LKB1 overexpression inhibits the proliferation, migration, invasion, epithelial-mesenchymal transition and angiogenesis of human lung cancer A549 cells, which may become a potential target for lung cancer treatment.
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