Environmental microcystin exposure triggers the poor prognosis of prostate cancer: Evidence from case-control, animal, and in vitro studies  

作　　者：Chun Pan Haixiang Qin Minghao Yan Xuefeng Qiu Wenyue Gong Wenxin Luo Hongqian Guo Xiaodong Han 

机构地区：[1]Immunology and Reproduction Biology Laboratory&State Key Laboratory of Analytical Chemistry for Life Science,Medical School,Nanjing University,Nanjing 210093,China [2]Jiangsu Key Laboratory of Molecular Medicine,Nanjing University,Nanjing 210093,China [3]Department of Urology,Drum Tower Hospital,Medical School of Nanjing University,Institute of Urology,Nanjing University,Nanjing 210008,China

出　　处：《Journal of Environmental Sciences》2023年第5期69-81,共13页环境科学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.31870492,31901182);the Natural Science Foundation of Jiangsu Province of China(No.BK20190316).

摘　　要：Microcystin-leucine-arginine(MC-LR)is positively linked with multiple cancers in humans.However,the association between MC-LR and the risk and prognosis of prostate cancer has not been conducted in epidemiological studies.No reported studies have linked MC-LR exposure to the poor prognosis of prostate cancer by conducting experimental studies.The content of MC-LR was detected in most of the aquatic food in wet markets and supermarkets in Nanjing and posed a health risk for consumers.MC-LR levels in both prostate cancer tissues and serum were significantly higher than controls.The adjusted odds ratio(OR)for prostate cancer risk by serum MC-LR was 1.75(95%CI:1.21-2.52)in the whole subjects,and a positive correlation between MC-LR and advanced tumor stage was observed.Survival curve analysis indicated patients with higher MC-LR levels in tissues exhibited poorer overall survival.Human,animal,and cell studies confirmed that MC-LR exposure increases the expression of estrogen receptor-α(ERα)and promotes epithelial-mesenchymal transition(EMT)in prostate cancer.Moreover,MC-LR-induced decreased E-cadherin levels,increased vimentin levels,and increased migratory and invasive capacities of prostate cancer cells were markedly suppressed upon ERαknockdown.MC-LR-induced xenograft tumor growth and lungmetastasis in BALB/c nude mice can be effectively alleviated with ERαknockdown.Our data demonstrated that MC-LR upregulated vimentin and downregulated E-cadherin through activating ERα,promoting migration and invasion of prostate cancer cells.Our findings highlight the role of MC-LR in prostate cancer,providing new perspectives to understand MC-LR-induced prostatic toxicity.

关 键 词：Microcystin-leucine-arginine (MC-LR) Estrogen receptor-α(ERα) Epithelial-mesenchymal transition (EMT) Prostate cancer E-cadherin Vimentin 

分 类 号：R737.25[医药卫生—肿瘤] X503.1[医药卫生—临床医学]