环境微囊藻毒素暴露引发前列腺癌的不良预后:来自病例对照、动物和体外研究的证据

IF 6.9 Q1 Environmental Science
Chun Pan , Haixiang Qin , Minghao Yan , Xuefeng Qiu , Wenyue Gong , Wenxin Luo , Hongqian Guo , Xiaodong Han
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引用次数: 4

摘要

微囊藻毒素亮氨酸精氨酸(MC-LR)与人类多种癌症呈正相关。然而,MC-LR与前列腺癌症的风险和预后之间的相关性尚未在流行病学研究中进行。没有报告的研究通过进行实验研究将MC-LR暴露与前列腺癌症的不良预后联系起来。在南京的湿货市场和超市的大多数水产食品中都检测到MC-LR的含量,这对消费者的健康构成了风险。前列腺癌症组织和血清中MC-LR水平均显著高于对照组。在整个受试者中,血清MC-LR对前列腺癌症风险的校正比值比(OR)为1.75(95%CI:1.21-2.52),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。人类、动物和细胞研究证实,MC-LR暴露增加了雌激素受体-α(ERα)的表达,并促进了前列腺癌症上皮-间质转化(EMT)。此外,MC-LR诱导的E-钙粘蛋白水平降低,波形蛋白水平升高,以及前列腺癌症细胞迁移和侵袭能力增加,在ERα敲低后受到显著抑制。敲低ERα可以有效减轻MC-LR诱导的BALB/c裸鼠异种移植物肿瘤生长和肺转移。我们的数据表明,MC-LR通过激活ERα,促进前列腺癌症细胞的迁移和侵袭,上调波形蛋白,下调E-钙粘蛋白。我们的研究结果强调了MC-LR在前列腺癌症中的作用,为理解MC-LR诱导的前列腺毒性提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Environmental microcystin exposure triggers the poor prognosis of prostate cancer: Evidence from case-control, animal, and in vitro studies

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.

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来源期刊
Journal of environmental sciences
Journal of environmental sciences Environmental Science (General)
CiteScore
12.80
自引率
0.00%
发文量
0
审稿时长
17 days
期刊介绍: Journal of Environmental Sciences is an international peer-reviewed journal established in 1989. It is sponsored by the Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, and it is jointly published by Elsevier and Science Press. It aims to foster interdisciplinary communication and promote understanding of significant environmental issues. The journal seeks to publish significant and novel research on the fate and behaviour of emerging contaminants, human impact on the environment, human exposure to environmental contaminants and their health effects, and environmental remediation and management. Original research articles, critical reviews, highlights, and perspectives of high quality are published both in print and online.
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