2. Academic Validation
  3. Environmental exposure to microcystin-LR increases the risks of urinary bladder proliferation and carcinogenesis: Evidence from case control, animal, and in vitro studies

Environmental exposure to microcystin-LR increases the risks of urinary bladder proliferation and carcinogenesis: Evidence from case control, animal, and in vitro studies

  • Toxicology. 2022 Oct;480:153326. doi: 10.1016/j.tox.2022.153326.
Chun Pan 1,  Haixiang Qin 2,  Haibo Jin 1,  Wenyuan Chen 2,  Hongqian Guo 3,  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; Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu, 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; Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu, China.
  • 3 Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, China; Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu, China. Electronic address: dr.ghq@nju.edu.cn.
  • 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; Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu, China. Electronic address: hanxd@nju.edu.cn.
PMID: 36115647 DOI: 10.1016/j.tox.2022.153326
Abstract

To date, no reported studies have explored the impacts of microcystin-LR (MC-LR) on bladder tissues, and even the occurrence of bladder Cancer. The current study explores the role of MC-LR in the development of bladder Cancer through human observation and experimental research. In the population study, the odds ratio of bladder Cancer for MC-LR was 6.073 (95 % CI, 2.117-17.422) after adjusting interference confounders. MC-LR is mainly located in the nucleus of epithelial cells in bladder Cancer tissues instead of normal tissues. A positive association was observed between MC-LR and advanced tumor stage in serum and tissues. The animal study confirmed that prolonged MC-LR treatment promoted the bladder Cancer phenotype accompanied by urinary bladder proliferation. In vitro, we indicated that MC-LR activated the PI3K/Akt/GSK3β/Cyclin D1 and JAK2/STAT3/Bcl2 signaling pathways to induce the growth of SV-HUC-1 cells. Moreover, MC-LR promoted the angiogenesis of SV-HUC-1 cells through PI3K/Akt/mTOR/HIF-1α/VEGF pathway. Our study provided the first evidence that prolonged MC-LR treatment increases the incidence of bladder Cancer from human investigations, mice models, and in vitro studies, implying the profound importance of the investigation of MC-LR for public health.

Keywords

Angiogenesis; Bladder cancer; MC-LR; Proliferation.

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