1. Academic Validation
  2. Environment relevant exposure of perfluorooctanoic acid accelerates the growth of hepatocellular carcinoma cells through mammalian target of rapamycin (mTOR) signal pathway

Environment relevant exposure of perfluorooctanoic acid accelerates the growth of hepatocellular carcinoma cells through mammalian target of rapamycin (mTOR) signal pathway

  • Environ Pollut. 2023 Nov 13:122910. doi: 10.1016/j.envpol.2023.122910.
Jiawei Hong 1 Xiaoyan Wang 2 Hangbiao Jin 3 Yuanchen Chen 3 Yifan Jiang 1 Keyi Du 1 Diyu Chen 1 Shusen Zheng 1 Linping Cao 4
Affiliations

Affiliations

  • 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, PR China; Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310003, PR China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, PR China.
  • 2 Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310003, PR China.
  • 3 Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, PR China.
  • 4 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, PR China; Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310003, PR China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, PR China. Electronic address: caolinping510@zju.edu.cn.
Abstract

Perfluorooctanoic acid (PFOA), a synthetic alkyl chain fluorinated compound, has emerged as a persistent organic pollutant of grave concern, casting a shadow over both ecological integrity and humans. Its insidious presence raises alarms due to its capacity to bioaccumulate within the human liver, potentially paving the treacherous path toward liver Cancer. Yet, the intricate mechanisms underpinning PFOA's role in promoting the growth of hepatocellular carcinoma (HCC) remain shrouded in ambiguity. Here, we determined the proliferation and transcription changes of HCC after PFOA exposure through integrated experiments including Cell Culture, nude mice tests, and colony-forming assays. Based on our findings, PFOA effectively promotes the proliferation of HCC cells within the experimental range of concentrations, both in vivo and in vitro. The proliferation efficiency of HCC cells was observed to increase by approximately 10% due to overexposure to PFOA. Additionally, the Cancer weight of tumor-bearing nude mice increased by 87.0% (p < 0.05). We systematically evaluated the effects of PFOA on HCC cells and found that PFOA's exposure can selectively activate the PI3K/Akt/mTOR/4E-BP1 signaling pathway, thereby playing a pro-cancer effect on HCC cells Confirmation echoed through western blot assays and inhibitor combination analyses. These insights summon a response to PFOA's dual nature as both an environmental threat and a promoter of liver Cancer. Our work illuminates the obscured domain of PFOA-induced hepatoxicity, shedding LIGHT on its ties to hepatocellular carcinoma progression.

Keywords

Cell proliferation; Hepatocellular carcinoma; PFOA; mTOR pathway.

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