Perfluorooctane sulfonate promotes the migration of colorectal cancer cells by inducing epithelial-mesenchymal transition  

作　　者：Fangfang Li Lu Chen Bi-Xia Peng Yuyang Lei Minjie Li Liang-Hong Guo 

机构地区：[1]Institute of Environmental and Health Sciences,China Jiliang University,Hangzhou 310018,China [2]Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province,Hangzhou 310015,China [3]College of Quality and Safety Engineering,China Jiliang University,Hangzhou 310018,China [4]College of Life Sciences,China Jiliang University,Hangzhou 310018,China

出　　处：《Journal of Environmental Sciences》2024年第11期1-12,共12页环境科学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.U20A20133);the Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province(No.20220207);the Fundamental Research Funds for the Provincial Universities of Zhejiang(No.2021YW63).

摘　　要：The potential association between colorectal cancer(CRC)and environmental pollutants is worrisome.Previous studies have found that some perfluoroalkyl acids,including perfluorooctane sulfonate(PFOS),induced colorectal tumors in experimental animals and promoted the migration of and invasion by CRC cells in vitro,but the underlying mechanism is unclear.Here,we investigated the effects of PFOS on the proliferation and migration of CRC cells and the potentialmechanisms involving activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition(EMT).It was found that PFOS promoted the growth andmigration of HCT116 cells at non-cytotoxic concentrations and increased the mRNA expression of the migration-related angiogenic cytokines vascular endothelial growth factor(VEGF)and interleukin-8(IL-8).In a mechanistic investigation,the up-stream signal pathway PI3K/Akt-NF-κB was activated by PFOS,and the process was suppressed by LY294002(PI3K/Akt inhibitor)and BAY11-7082(NF-κB inhibitor)respectively,leading to less proliferation of HCT116 cells.Furthermore,matrix metalloproteinases(MMP)and EMT-related markers were up-regulated after PFOS exposure,and were also suppressed respectively by LY294002 and BAY11-7082.Moreover,the up-regulation of EMT markers was suppressed by a MMP inhibitor GM6001.Taken together,our results indicated that PFOS promotes colorectal cancer cell migration and proliferation by activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition.This could be a potential toxicological mechanism of PFOS-induced malignant development of colorectal cancer.

关 键 词：Perfluorooctane sulfonate Colorectal cancer Cell migration PI3K/Akt-NF-κB Epithelial-mesenchymal transition 

分 类 号：X503.1[环境科学与工程—环境工程]