目的 探讨臭牡丹总黄酮对人肺癌A549细胞增殖、迁移和侵袭的作用及其机制。方法 将pcDNA3.1+空载体与S45位点突变的β-链蛋白（S45A-β-catenin）真核过表达载体转染A549细胞，给予臭牡丹总黄酮干预。MTT法检测细胞的相对存活率，划痕实验检测细胞迁移能力，Transwell小室侵袭实验检测细胞的侵袭能力，Western blotting法检测各组细胞β-catenin、上皮细胞钙黏蛋白（E-cadherin）、波形蛋白（vimentin）、转录因子Snail 2（Slug）、糖原合成酶激酶-3β（GSK-3β）、p-GSK-3β的表达水平。结果 转染S45A-β-catenin质粒后，A549细胞增殖、迁移、侵袭能力均明显增强，β-catenin、vimentin蛋白表达水平显著上调，E-cadherin、GSK-3β、P-GSK-3β蛋白的表达水平显著下调。臭牡丹总黄酮可抑制A549细胞的增殖、迁移与侵袭能力，对转染S45A-β-catenin质粒组的细胞作用尤为明显。对转染空载质粒的A549细胞，可上调E-cadherin、GSK-3β、P-GSK-3β表达，下调β-catenin、vimentin表达；对转染S45A-β-catenin质粒的A549细胞，可下调β-catenin、vimentin表达。结论 抑制细胞中β-catenin的高表达并调控下游的一系列因子，从而影响Wnt/β-catenin通路诱导的上皮间质转化（EMT）现象可能是臭牡丹总黄酮抑制肺癌侵袭、转移的重要作用机制之一。

Objective To observe the effect of the total flavonoids of Clerodendrum Bungei (TFCB) on proliferation, invasion and migration of A549 cell lines by Wnt/β-catenin signal pathway.Methods Transfecting A549 cell lines with empty vector pcDNA3.1 and β-catenin plasmid which has the mutation at S45 (S45A-β-catenin), which were intervened with TFCB. MTT assay detected cell proliferation, scratch test observed cell migration, Transwell experiment detected the cell invasion. The expression of β-catenin, E-Cadherin, vimentin, Slug, GSK-3β, and p-GSK-3β protein in each group was detected by Western blotting.Results The proliferation, invasion and migration of A549 cells were enhanced significantly after transfected with S45A-β-catenin plasmid (P < 0.05 or 0.01), along with the increasing expression of β-catenin, vimentin, and the reducing expression of E-cadherin, GSK-3β, P-GSK-3β (P < 0.01). TFCB can inhibit the proliferation, migration and invasion of A549 cells (P < 0.05), expecially in S45A-β-catenin group (P < 0.001). A549 cells transfected with empty vector had the ability of up-regulating the expression of E-cadherin, GSK-3β and P-GSK-3β, down-regulating the expression of β-catenin and vimentin with TFCB. A549 cells transfected with S45A-β-catenin plasmid had the ability of down-regulating the expression of β-catenin and vimentin with TFCB.Conclusion The mechanism of inhibiting lung cancer of TFCB maybe associate with the inhibitory expression of β-catenin and regulate the downstream factors, with view to inducing EMT by activating Wnt/β-catenin pathway.

国家自然科学基金资助项目（81503452）；湖南省自然科学基金（14JJ4066）；湖南省教育厅项目（13C674）