Tris(2‐chloroethyl)phosphate‐induced cell growth arrest via attenuation of SIRT1‐independent PI3K/Akt/mTOR pathway
Tris(2‐chloroethyl)phosphate‐induced cell growth arrest via attenuation of SIRT1‐independent PI3K/Akt/mTOR pathway
复制标题
DOI：
10.1002/jat.3223
复制
发表时间：
2016-07
影响因子：
3.3
通讯作者：
Wenjuan Zhang;Youjian Zhang;Zhiyuan Wang;T. Xu;Cheng Huang;Wenjun Yin;Jing Wang;W. Xiong;Wenhong Lu;Hongyan Zheng;Jing-Jue Yuan
中科院分区：
文献类型：
--
作者：
Wenjuan Zhang;Youjian Zhang;Zhiyuan Wang;T. Xu;Cheng Huang;Wenjun Yin;Jing Wang;W. Xiong;Wenhong Lu;Hongyan Zheng;Jing-Jue Yuan
磷酸三（2-氯乙基）酯（TCEP）作为一种有机磷阻燃剂和增塑剂，已广泛应用于工业和家用产品中。它不仅在住宅室内空气和灰尘、地表水和饮用水中被检测到，而且在人类血浆和母乳以及啮齿动物的肝脏、肾脏和大脑组织样本中也被检测到。TCEP被归类为致癌类别2和生殖毒性类别1B。来自实验动物的充分证据表明TCEP在肝脏和肾脏中的致癌性以及脑中的细胞损失。然而，TCEP诱导肝毒性的潜在机制大多未知。我们研究了TCEP的体外作用以及TCEP通过PI 3 K/Akt/mTOR途径诱导的L02和HepG 2细胞生长。我们发现，TCEP降低这些细胞系的细胞活力，诱导细胞生长停滞，上调SIRT 1的mRNA和蛋白水平，并减弱PI 3 K/Akt/mTOR通路。然而，在用EX-527抑制SIRT 1表达后，L02和HepG 2细胞的生长停滞加重。上述结果表明，TCEP通过减弱SIRT 1非依赖性PI 3 K/Akt/mTOR通路诱导L02和HepG 2细胞生长停滞。版权所有© 2015约翰威利父子有限公司.
Tris(2‐chloroethyl)phosphate (TCEP) as an organophosphorus flame retardant and plasticizer has been widely used in industrial and household products. It not only was detected in residential indoor air and dust, surface and drinking water, but also in human plasma and breast milk, and tissue samples of liver, kidneys and brain from rodents. TCEP is classified as carcinogenic category 2 and toxic for reproduction category 1B. Sufficient evidence from experimental animals indicated carcinogenicity of TCEP in the liver, and kidneys as well as cell loss in the brain. However, the underlying mechanisms of TCEP‐induced hepatotoxicity are mostly unknown. We investigated the in vitro effects of TCEP as well as TCEP‐induced cell growth in the L02 and HepG2 cells through the PI3K/Akt/mTOR pathway. We found that TCEP reduced cell viability of these cell lines, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway. However, growth arrest of the L02 and HepG2 cells were aggravated after inhibiting the SIRT1 expression with EX‐527. The findings above suggested that TCEP induced the cell growth arrest of L02 and HepG2 cells via attenuation of the SIRT1‐independent PI3K/Akt/mTOR pathway. Copyright © 2015 John Wiley & Sons, Ltd.