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三氯生可增强抗失巢凋亡的人肺癌细胞的上皮-间质转化。

Triclosan potentiates epithelial-to-mesenchymal transition in anoikis-resistant human lung cancer cells.

作者信息

Winitthana Thidarat, Lawanprasert Somsong, Chanvorachote Pithi

机构信息

Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

出版信息

PLoS One. 2014 Oct 16;9(10):e110851. doi: 10.1371/journal.pone.0110851. eCollection 2014.

Abstract

Alteration of cancer cell toward mesenchymal phenotype has been shown to potentiate tumor aggressiveness by increasing cancer cell metastasis. Herein, we report the effect of triclosan, a widely used antibacterial agent found in many daily products, in enhancing the epithelial-to-mesenchymal transition (EMT) in aggressive anoikis resistant human H460 lung cancer cells. EMT has been long known to increase abilities of the cells to increase migration, invasion, and survival in circulating system. The present study reveals that treatment of the cancer cells with triclosan at the physiologically related concentrations significantly increased the colony number of the cancer cells assessed by tumor formation assay. Also, the mesenchymal-like morphology and decrease in cell-to-cell adhesion were observed in triclosan-treated cells. Importantly, western blot analysis revealed that triclosan-treated cells exhibited decreased E-cadherin, while the levels of EMT markers, namely N-cadherin, vimentin, snail and slug were found to be significantly up-regulated. Furthermore, EMT induced by triclosan treatment was accompanied by the activation of focal adhesion kinase/ATP dependent tyrosine kinase (FAK/Akt) and Ras-related C3 botulinum toxin substrate 1 (Rac1), which enhanced the ability of the cells to migrate and invade. In conclusion, we demonstrated for the first time that triclosan may potentiate cancer cells survival in detached condition and motility via the process of EMT. As mentioned capabilities are required for success in metastasis, the present study provides the novel toxicological information and encourages the awareness of triclosan use in cancer patients.

摘要

癌细胞向间充质表型的转变已被证明可通过增加癌细胞转移来增强肿瘤侵袭性。在此,我们报告了三氯生(一种在许多日常用品中广泛使用的抗菌剂)对侵袭性失巢凋亡抗性人H460肺癌细胞上皮-间质转化(EMT)的增强作用。长期以来,人们一直知道EMT会增加细胞在循环系统中的迁移、侵袭和存活能力。本研究表明,用生理相关浓度的三氯生处理癌细胞,通过肿瘤形成试验评估,显著增加了癌细胞的集落数量。此外,在三氯生处理的细胞中观察到间充质样形态和细胞间粘附的减少。重要的是,蛋白质印迹分析显示,三氯生处理的细胞中E-钙粘蛋白减少,而EMT标志物N-钙粘蛋白、波形蛋白、蜗牛蛋白和蛞蝓蛋白的水平显著上调。此外,三氯生处理诱导的EMT伴随着粘着斑激酶/ATP依赖性酪氨酸激酶(FAK/Akt)和Ras相关C3肉毒杆菌毒素底物1(Rac1)的激活,这增强了细胞的迁移和侵袭能力。总之,我们首次证明三氯生可能通过EMT过程增强癌细胞在脱离状态下的存活和运动能力。由于转移成功需要上述能力,本研究提供了新的毒理学信息,并促使人们关注癌症患者中三氯生的使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d534/4199721/d3039b8d95ef/pone.0110851.g001.jpg

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