大叶茜草素抑制肺癌A549、H1299细胞增殖和迁移的机制研究

Inhibition mechanism of mollugin on the proliferation and migration of A549 and H1299 cells

目的:观察大叶茜草素对肺癌A549、H1299细胞增殖和迁移的作用,探讨其抑制肿瘤细胞可能的分子机制。方法:在体外培养肺癌A549、H1299细胞,加入大叶茜草素共同培养,采用MTT实验和细胞划痕实验探究细胞增殖和迁移的变化情况;利用蛋白质印迹法检测细胞上皮-间充质转化(EMT)蛋白(Fibronectin、E-cadherin、Vimentin、Snail)和Wnt/β-catenin信号通路蛋白(GSK-3β、pGSK-3β、β-catenin)的表达情况。结果:大叶茜草素对A549、H1299细胞的增殖和迁移具有显著抑制作用,并且其抑制增殖作用与药物浓度呈依赖性(P<0.05)。细胞划痕实验48 h后,加药组A549、H1299细胞的迁移均受到抑制(P<0.05)。蛋白质印迹实验结果显示,大叶茜草素作用后,Fibronectin、Vimentin、Snail、pGSK-3β(失活型)、β-catenin蛋白表达受到抑制,而E-cadherin蛋白表达上升(P<0.05)。结论:大叶茜草素具有抑制肺癌A549、H1299细胞的增殖与迁移作用,其机制可能与抑制Wnt/β-catenin信号通路并导致EMT进程受阻有关。

Objective:To observe the effect of mollugin on the proliferation and migration of lung cancer A549 and H1299 cells, and explore the molecular mechanism of this extract in inhibiting tumor cells.Methods:Human A549 and H1299 cells were cultured with molligin in vitro.MTT assay and wound healing test were performed to observe the effect of mollugin on proliferation and migration of the cells.Western blot was used to detect the expression of mollugin on epithelial-mesenchymal-transition(EMT)-related proteins(including fibronectin, E-cadherin, vimentina and snail) and Wnt/β-catenin signaling pathway proteins(including GSK-3β,pGSK-3β and β-catenin).Results:Mollugin notably inhibited the proliferation and migration of A549 and H1299 cells, and the inhibition on proliferation presented in a dose-dependent manner with the drug dose(P<0.05).Western blotting results showed that the expression of fibronectin, vimentin, and snail protein was decreased, yet the expression of E-cadherin protein was up-regulated, and the protein expression of pGSK-3β and β-catenin was decreased after mollugin treatment(P<0.05).Conclusion:Mollugin can inhibit the proliferation and migration of lung cancer A549 and H1299 cells.The mechanism may be related to inhibition of Wnt/β-catenin signaling pathway and obstruction of EMT process.