唑来膦酸对食管鳞癌细胞转移的抑制作用

Inhibition Effect of Zoledronic Acid on Metastasis of Esophagus Squamous Cell Carcinoma

目的分析唑来膦酸(ZOL)对食管鳞癌细胞转移能力的抑制效应并探讨其分子机制。方法食管鳞癌细胞株EC9706与EC109细胞经ZOL处理后,以噻唑蓝(MTT)比色法测定细胞增殖能力,细胞侵袭与划痕愈合实验检测细胞侵袭与转移能力,免疫印迹(Western blotting)、逆转录-聚合酶链反应(RT-PCR)与细胞免疫荧光实验检测转移相关蛋白表达变化。结果不同浓度ZOL处理可显著抑制EC9706与EC109细胞的增殖、侵袭与迁移能力,同未加药对照组比较,均差异有统计学意义(P<0.05);ZOL处理通过抑制转录因子Slug转录上调紧密连接蛋白表达水平,转染因子Slug可逆转ZOL的抗细胞转移效应。结论 ZOL通过Slug调控紧密连接蛋白表达可能是其干预食管鳞癌细胞转移的分子机制。

Objective To examine the inhibition effect of zoledronic acid （ ZOL） on malignant metastasis of human esophagus squamous cell carcinoma （ ESCC） cells and to analyze its molecular mechanisms. Methods EC9706 and EC109 cells were treated with ZOL,and then MTT assay,adhesion and invasion assay were performed to observe the inhibitor effect of As2O3 on proliferation and metastasis of esophagus carcinoma cells.The expression of metastasis-related proteins was detected by Western blotting. Results Exposure to ZOL significantly presented suppressive functions on growth and metastasis of both kinds of cancer cells,in a dose-dependent manner（ P 〈0.05）.Additionally,the expression level of occludin was increased after ZOL treatment by suppressing transcriptional factor Slug.Transfection of Slug could reverse anti-metastasis of ZOL. Conclusion ZOL possesses a significant anti-metastasis function on ESCC cells, mainly through repressing Slug to restore occludin expression.