中国科学家发现肝癌发病新机制
Published:11 May2018    Source:http://www.cncbd.org.cn/News/Detail/7547

新华社华盛顿4月18日电(记者周舟)18日发表在美国《科学·转化医学》杂志上的一篇论文揭示了非酒精性脂肪肝诱发肝癌的一种发病机制。文章说,已获美国食品和药物管理局批准的一种抗真菌药物或有预防和治疗这类肝癌的功效。

 

肝脏脂肪细胞堆积导致的非酒精性脂肪肝是全球最严重的公共健康问题之一,三到四成的成年人受这种疾病危害,并可能发展为肝硬化和肝癌。

 

中国香港中文大学医学院内科与治疗学系于君教授与刘大斌等研究人员一起,对非酒精性脂肪肝诱发的肝癌肿瘤组织和癌旁肝脏组织的基因组表达进行了分析,发现肝癌发生时肝细胞内“角鲨烯环氧化酶”表达水平显著提高。

 

于君对新华社记者说,“角鲨烯环氧化酶”是人体内合成胆固醇的关键酶,其过度表达会促进肝细胞胆固醇酯堆积和氧化应激水平升高,后者改变了细胞内甲基化水平,从而促进肝癌发生和发展。

 

研究人员构建了肝细胞高表达“角鲨烯环氧化酶”的转基因实验小鼠模型,并投喂高胆固醇、高脂肪食品。结果显示,与野生小鼠相比,实验小鼠肝癌发病率显著升高,提示“角鲨烯环氧化酶”可能是非酒精性脂肪肝诱发肝癌的潜在治疗靶标。

 

实验还发现,一种常用的抗真菌药“特比萘芬”可有效抑制“角鲨烯环氧化酶”的表达,并明显抑制由这种酶介导的肿瘤细胞生长和肝癌发生,显著延长肝癌小鼠的生存期。研究人员认为,这种药的作用机理是降低肝细胞胆固醇酯堆积和氧化应激水平。

 

于君说,新发现为非酒精性脂肪肝诱发肝癌的预防和治疗提供了新的实验基础和方向。

 

来源: 新华社

供稿:公共卫生处

 

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