کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5860494 1133187 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dichlorodiphenyltrichloroethane exposure induces the growth of hepatocellular carcinoma via Wnt/β-catenin pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Dichlorodiphenyltrichloroethane exposure induces the growth of hepatocellular carcinoma via Wnt/β-catenin pathway
چکیده انگلیسی


- Low doses p,p′-DDT exposure promotes the proliferation of HepG2 cells.
- Both oxidative stress and Wnt/β-catenin pathway act as pivotal player in p,p′-DDT-induced proliferation of HepG2 cells.
- The stimulation of Wnt/β-catenin pathway is mediated by oxidative stress.
- p,p′-DDT treatment increased the growth of tumor in nude mice.

Dichlorodiphenyltrichloroethane (DDT) is a persistent organic pollutant, involved in the progression of many cancers, including liver cancer. However, the underlying mechanism(s) of DDT, especially how low doses DDT cause liver cancer, is poorly understood. In this study, we evaluated the impact of p,p′-DDT on the growth of hepatocellular carcinoma using both in vitro and in vivo models. The present data indicated that the proliferation of HepG2 cells was strikingly promoted after exposed to p,p′-DDT for 4 days. In addition, reactive oxygen species (ROS) content was significantly elevated, accompanied with inhibitions of γ-glutamylcysteine synthetase (γ-GCS) and superoxide dismutase (SOD) activities. Interestingly, the levels of β-catenin and its downstream target genes (c-Myc and CyclinD1) were significantly up-regulated, and co-treatment of NAC, the ROS inhibitor, inhibited these over-expressed proteins. Moreover, the p,p′-DDT-stimulated proliferation of HepG2 cells could be reversed after NAC or β-catenin siRNA co-treatment. Likewise, p,p′-DDT treatment increased the growth of tumor in nude mice, stimulated oxidative stress and Wnt/β-catenin pathway. Our study indicates that low doses p,p′-DDT exposure promote the growth of hepatocellular carcinoma via Wnt/β-catenin pathway which is activated by oxidative stress. The finding suggests an association between low dose DDT exposure and liver cancer growth.

p′-DDT exposed to hepatocellular carcinoma, first activates ROS and stimulates the oxidative stress. Next, it promotes phosphorylation of GSK3βat Ser 9. Afterwards, active β-catenin enters the nucleus and binds to the transcription factor TCF, which regulates expression of its downstream target genes (c-Myc and CyclinD1). These downstream targets are associated with proliferation, thus promoting the growth of hepatocellular carcinoma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 225, Issue 1, 10 February 2014, Pages 158-166
نویسندگان
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