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.
Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, China.
J Environ Sci (China). 2023 May;127:69-81. doi: 10.1016/j.jes.2022.05.051. Epub 2022 Jun 8.
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 ERα knockdown. MC-LR-induced xenograft tumor growth and lung metastasis in BALB/c nude mice can be effectively alleviated with ERα knockdown. 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.
微囊藻毒素-亮氨酸-精氨酸（MC-LR）与人类的多种癌症呈正相关。然而，流行病学研究尚未探讨 MC-LR 与前列腺癌风险和预后之间的关系。没有研究通过实验研究将 MC-LR 暴露与前列腺癌的不良预后联系起来。在南京的农贸市场和超市的大部分水生食品中都检测到了 MC-LR 的含量，这对消费者的健康构成了威胁。前列腺癌组织和血清中的 MC-LR 水平明显高于对照组。在全人群中，血清 MC-LR 与前列腺癌风险的调整比值比（OR）为 1.75（95%CI：1.21-2.52），并且观察到 MC-LR 与晚期肿瘤分期呈正相关。生存曲线分析表明，组织中 MC-LR 水平较高的患者总体生存率较差。人体、动物和细胞研究证实，MC-LR 暴露会增加前列腺癌细胞中雌激素受体-α（ERα）的表达，并促进上皮间质转化（EMT）。此外，MC-LR 诱导的 E-钙黏蛋白水平降低、波形蛋白水平升高以及前列腺癌细胞迁移和侵袭能力增强，在 ERα 敲低后明显受到抑制。MC-LR 诱导的 BALB/c 裸鼠异种移植肿瘤生长和肺转移可以通过 ERα 敲低得到有效缓解。我们的数据表明，MC-LR 通过激活 ERα 上调波形蛋白并下调 E-钙黏蛋白，促进前列腺癌细胞的迁移和侵袭。我们的研究结果强调了 MC-LR 在前列腺癌中的作用，为理解 MC-LR 诱导的前列腺毒性提供了新的视角。
