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  3. Chronic exposure to microcystin-LR increases the risk of prostate cancer and induces malignant transformation of human prostate epithelial cells

Chronic exposure to microcystin-LR increases the risk of prostate cancer and induces malignant transformation of human prostate epithelial cells

  • Chemosphere. 2021 Jan;263:128295. doi: 10.1016/j.chemosphere.2020.128295.
Chun Pan 1,  Ling Zhang 1,  Xiannan Meng 1,  Haixiang Qin 2,  Zou Xiang 3,  Wenyue Gong 1,  Wenxin Luo 1,  Dongmei Li 1,  Xiaodong Han 4
Affiliations

Affiliations

  • 1 Immunology and Reproduction Biology Laboratory, State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, China.
  • 2 Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.
  • 3 Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
  • 4 Immunology and Reproduction Biology Laboratory, State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, China. Electronic address: [email protected].
PMID: 33297237 DOI: 10.1016/j.chemosphere.2020.128295
Abstract

Microcystins-LR (MC-LR) acts as a possible carcinogen for humans and causes a serious risk to public environmental health. The current study aimed to evaluate the interaction between MC-LR exposure and prostate Cancer development and elucidate the underlying mechanism. In this study, mice were exposed to MC-LR at various doses for 180 days. MC-LR was able to induce the progression of prostatic intraepithelial neoplasia (PIN) and microinvasion. Furthermore, MC-LR notably increased angiogenesis and susceptibility to prostate Cancer in vivo. In vitro, over 25 weeks of MC-LR exposure, normal human prostate epithelial (RWPE-1) cells increased secretion of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and colony formation, features typical for Cancer cells. These MC-LR-transformed prostate epithelial cells displayed increased expression of forkhead box M1 (FOXM1) and cyclooxygenase-2 (COX-2); abrogation of FOXM1 or COX-2 activity by specific inhibitors could abolish the invasion and migration of MC-LR-treated cells. In conclusion, we have provided compelling evidence demonstrating the induction of a malignant phenotype in human prostate epithelial cells and the in vivo development of prostate Cancer by exposure to MC-LR, which might be a potential tumor promoter in the progression of prostate Cancer.

Keywords

COX-2; FOXM1; MC-LR; Prostate cancer.

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