title: The evaluation of p,p'-DDT exposure on cell adhesion of hepatocellular carcinoma.
abstract: Many studies have found a positive association between the progression of hepatocellular carcinoma and DDT exposure. These studies mainly focus on the effect of DDT exposure on cell proliferation and epithelial to mesenchymal transition (EMT) promotion. However, the influence of DDT on cell adhesion of hepatocellular carcinoma remains to be unclear. The aim of our study was to determine the effect of p,p'-DDT on cell adhesion of hepatocellular carcinoma in vitro and in vivo. The data showed that p,p'-DDT, exposing HepG2 cells for 6 days, decreased cell-cell adhesion and elevated cell-matrix adhesion. Strikingly, p,p'-DDT increased reactive oxygen species (ROS) content, and this was accompanied by the activation of JAK/STAT3 pathway. Moreover, ROS inhibitor supplement reversed these effects significantly. However, the addition of ER inhibitor, ICI, had no effect on the p,p'-DDT-induced effects. p,p'-DDT altered the mRNA levels of related adhesion molecules, including inhibition of E-cadherin and promotion of N-cadherin along with CD29. Interestingly, the p,p'-DDT-altered adhesion molecules could be reversed with JAK inhibitor or STAT3 inhibitor. Likewise, p,p'-DDT stimulated the JAK/STAT3 pathway in nude mice, as well as altered the mRNA levels of E-cadherin, N-cadherin, and CD29. Taken together, these results indicate that p,p'-DDT profoundly promotes the adhesion process by decreasing cell-cell adhesion and inducing cell-matrix adhesion via the ROS-mediated JAK/STAT3 pathway. All these events account for the carcinogenic potential of p,p'-DDT in liver.
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: Xiaoting
authors.initials: X
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.
authors.forename: Meilan
authors.initials: M
authors.lastname: Chen
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: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: College of Life Science, Shanxi University, Taiyuan 030006, China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Li
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: lzy@sxu.edu.cn.
authors.forename: Zhuoyu
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D045744:Cell Line, Tumor; D003634:DDT / Q000633:toxicity*; D004721:Endoplasmic Reticulum / Q000187:drug effects; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D019012:Integrin beta1 / Q000096:biosynthesis; D053612:Janus Kinases / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D007306:Insecticides; D019012:Integrin beta1; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D003634:DDT; D053612:Janus Kinases
keywords: Cell adhesion; Hepatocellular carcinoma; JAK/STAT3 pathway; Oxidative stress; p,p′-DDT