title: Dichlorodiphenyltrichloroethane exposure induces the growth of hepatocellular carcinoma via Wnt/β-catenin pathway.
abstract: 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.
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Jin
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China; MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Zhao
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China; College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: jinxiaoting.2008@163.com.
authors.forename: Zhuo-Yu
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Research Center of Environmental Science, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Zhao
authors.affiliation: MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D003634:DDT / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018384:Oxidative Stress / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D002273:Carcinogens; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; D051176:beta Catenin; D019938:Cyclin D1; D003634:DDT; D013482:Superoxide Dismutase; D005721:Glutamate-Cysteine Ligase
keywords: Hepatocellular carcinoma; Proliferation; ROS; Wnt/β-catenin pathway; p,p′-DDT