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苯并(a)芘通过上调 Twist1 增强肺腺癌细胞 A549 的 EMT 相关迁移。

Benzo(a)pyrene enhances the EMT-associated migration of lung adenocarcinoma A549 cells by upregulating Twist1.

机构信息

Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

Department of Geriatrics, Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Oncol Rep. 2017 Oct;38(4):2141-2147. doi: 10.3892/or.2017.5874. Epub 2017 Aug 3.

Abstract

Benzo(a)pyrene (BaP), an important toxic component of cigarette smoke, can cause lung cancer and lead to the progression of lung cancer. In the present study, we investigated the effect of BaP on the migration of lung adenocarcinoma A549 cells. BaP (1 µM) promoted the migration of A549 cells in a time-dependent manner and upregulated the expression of the Twist family BHLH transcription factor 1 (Twist1). BaP also induced upregulation of the mesenchymal markers N-cadherin and vimentin and downregulation of the epithelial marker E-cadherin. When the expression of Twist1 was knocked down in A549 cells that were treated with BaP for 4 weeks (A549BaP-4w), the expression of Twist1 decreased, which inhibited the migration capacity of A549BaP-4w cells, the expression of N-cadherin and vimentin was downregulated and the expression of E-cadherin was upregulated. In addition, morphological observations of A549BaP-4w cells revealed that the epithelial characteristics of A549 cells became mesenchymal characteristics. When the expression of Twist1 was knocked down, the A549BaP-4w cells were transformed back to cells with epithelial characteristics. In conclusion, the results from the present study indicate that BaP enhances the epithelial-mesenchymal transition-associated migration of lung adenocarcinoma A549 cells by upregulating Twist1.

摘要

苯并(a)芘(BaP)是香烟烟雾中的一种重要有毒成分,可导致肺癌并促进肺癌的进展。在本研究中,我们研究了 BaP 对肺腺癌细胞 A549 迁移的影响。BaP(1µM)以时间依赖性方式促进 A549 细胞的迁移,并上调 Twist 家族 BHLH 转录因子 1(Twist1)的表达。BaP 还诱导间充质标志物 N-钙粘蛋白和波形蛋白的上调以及上皮标志物 E-钙粘蛋白的下调。当用 BaP 处理 4 周的 A549 细胞(A549BaP-4w)中 Twist1 的表达被敲低时,Twist1 的表达减少,抑制了 A549BaP-4w 细胞的迁移能力,下调了 N-钙粘蛋白和波形蛋白的表达,并上调了 E-钙粘蛋白的表达。此外,对 A549BaP-4w 细胞的形态观察表明,A549 细胞的上皮特征转变为间充质特征。当 Twist1 的表达被敲低时,A549BaP-4w 细胞被转化回具有上皮特征的细胞。总之,本研究结果表明,BaP 通过上调 Twist1 增强了肺腺癌细胞 A549 的上皮-间充质转化相关迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf3d/5652958/153782d39055/OR-38-04-2141-g00.jpg

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