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
Environmental microcystin exposure triggers the poor prognosis of prostate cancer: Evidence from case-control, animal, and in vitro studies
Chun Pan∗∗, Haixiang Qin∗∗, Minghao Yan, Xuefeng Qiu, Wenyue Gong, Wenxin Luo, Hongqian Guo∗, Xiaodong Han∗
https://doi.org/10.1016/j.jes.2022.05.051
摘要
MC-LR作为一类重要的环境污染物，目前尚没有其对前列腺癌发生影响的相关报道。因此，探究MC-LR暴露是否会引起前列腺癌的发生并在人群中开展流行病学调研具有重要的现实意义。首先我们评估了南京地区饮用水及水产品中MC-LR的污染情况，在农贸市场和超市的大部分水产中均检测到MC - LR的存在，对消费者存在健康风险。基于此，本文开展了MC-LR暴露与前列腺癌发生关联的病例对照研究，MC-LR在前列腺癌组织和血清中的水平均显著高于对照组。在整个研究对象中，血清MC - LR对前列腺癌风险的校正比值比为1.75 ( 95% CI : 1.21-2.52)，且MC-LR与晚期肿瘤分期呈正相关。生存曲线分析显示，前列腺癌组织中MC-LR水平较高的患者总体生存率较差。人群、动物和细胞研究证实，MC-LR暴露增加雌激素受体α的表达，促进上皮间充质转化，导致前列腺癌的发生。此外，敲低ERα后，可有效逆转MC-LR引起的E-cadherin表达降低、Vimentin表达升高及前列腺癌细胞的迁移和侵袭增强，缓解MC-LR诱导的BALB/c裸鼠移植瘤的生长和肺转移。本研究强调了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。
亮点
1. MC-LR在水产品中污染程度广泛
2. 血清MC-LR是前列腺癌发生的独立危险因素
3. 前列腺组织中MC-LR含量越高，患者预后越差，死亡率越高
Abstract
As an important environmental pollutant, MC-LR has not been reported to have an effect on prostate cancer. It is of great practical significance to explore whether chronic MC-LR exposure caused the occurrence of prostate cancer, and conduct a case-control study of serum MC-LR exposure and prostate cancer in the population to clarify the correlation between MC-LR exposure and the incidence of prostate cancer. 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.
作者简介
第一作者
潘春博士 于2022年在南京大学生命科学学院获得博士学位。现任扬州大学讲师，主要从事微囊藻毒素的泌尿和骨骼系统的毒理学研究，环境污染物通过肠道菌群调控远隔脏器等相关研究。在Theranostics，Environment pollution，Chemosphere等国际期刊发表文章10余篇。
通讯作者
韩晓冬博士于2004年在中科院生态环境研究中心获得工学博士学位，期间作为高级访问学者赴美国哈佛大学医学院Beth Israel Deaconess Medical Center开展合作研究。长期从事生殖与发育、环境污染与疾病发生、干细胞与组织再生研究，主持并参与国家自然科学基金、国家“973计划”、教育部博士点基金、江苏省自然科学基金等研究项目，在国内外学术刊物共发表论文210余篇。参编《组织胚胎学》、《生殖病理学》教材。主讲的“组织学与胚胎学”入选南京大学百门优质课程，被认定为省级一流本科课程。在Environ. Sci. Technol.，Environ. Health Perspect, J. Hazard. Mater., Autophagy, Environ. Int.等国际期刊上发表研究论文210多篇。
原文链接
https://www.sciencedirect.com/science/article/pii/S1001074222002996
引用格式
Chun Pan, Haixiang Qin, Minghao Yan, Xuefeng Qiu, Wenyue Gong, Wenxin Luo, Hongqian Guo, Xiaodong Han, 2023. Environmental microcystin exposure triggers the poor prognosis of prostate cancer: Evidence from case-control, animal, and in vitro studies. J. Environ. Sci. 127, 69-81.
