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甲基三氯生对人肝细胞L02细胞增殖和迁移的兴奋效应

Hormesis Effect of Methyl Triclosan on Cell Proliferation and Migration in Human Hepatocyte L02 Cells.

作者信息

An Jing, Yao Weiwei, Tang Waner, Jiang Jingjing, Shang Yu

机构信息

Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, P. R. China.

出版信息

ACS Omega. 2021 Jul 14;6(29):18904-18913. doi: 10.1021/acsomega.1c02127. eCollection 2021 Jul 27.

Abstract

Methyl triclosan (mTCS) is a methylated derivative of triclosan (TCS), which is extensively used as an antimicrobial component of various nursing products and disinfectants. Current research studies of mTCS mainly focused on the environmental persistence and bioaccumulation potential. Knowledge regarding the toxicity and carcinogenicity of mTCS is limited until now. In this study, the human hepatocyte L02 cells were used to investigate the cellular effects of mTCS under different concentrations (0.1-60 μM). The hormesis effect was observed where a low dose of mTCS (≤5 μM) exposure stimulated the cell proliferation ability, while high-dose exposure (≥20 μM) inhibited cell proliferation. In the same time, low doses of mTCS (0.5 and 1 μM) induced enhanced anchorage-independent proliferation ability and cell migration ability, indicating a positive effect on malignant transformation in L02 cells. Moreover, reactive oxygen species productions were significantly increased after mTCS exposure (≥1 μM), as compared with the control group. Furthermore, expressions of tumor-related genes, mouse double minute 2 (MDM2), matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (), and proto-oncogene MYC (), , and were significantly upregulated, while no significant changes were observed on expressions of apoptosis-related and cell cycle-related genes in L02 cells after exposure of low-dose mTCS. In conclusion, these results indicated that a low dose of mTCS had a hormesis effect in L02 cells on cell proliferation and malignant transformation , which might be mediated through oxidative stress response.

摘要

甲基三氯生(mTCS)是三氯生(TCS)的甲基化衍生物,三氯生被广泛用作各种护理产品和消毒剂的抗菌成分。目前关于mTCS的研究主要集中在其环境持久性和生物累积潜力方面。直到现在,关于mTCS毒性和致癌性的知识还很有限。在本研究中,使用人肝细胞L02细胞来研究不同浓度(0.1 - 60 μM)的mTCS对细胞的影响。观察到了 hormesis 效应,即低剂量的mTCS(≤5 μM)暴露刺激细胞增殖能力,而高剂量暴露(≥20 μM)则抑制细胞增殖。同时,低剂量的mTCS(0.5和1 μM)诱导了非锚定依赖性增殖能力和细胞迁移能力增强,表明对L02细胞的恶性转化有积极影响。此外,与对照组相比,mTCS暴露(≥1 μM)后活性氧生成显著增加。此外,肿瘤相关基因小鼠双微体2(MDM2)、基质金属蛋白酶9(MMP9)和增殖细胞核抗原()以及原癌基因MYC()、(此处原文可能有缺失)和(此处原文可能有缺失)的表达显著上调,而低剂量mTCS暴露后L02细胞中凋亡相关基因和细胞周期相关基因的表达未观察到显著变化。总之,这些结果表明低剂量的mTCS在L02细胞中对细胞增殖和恶性转化具有hormesis效应,这可能是通过氧化应激反应介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14c5/8320140/a30510ae1db4/ao1c02127_0002.jpg

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