低氧条件下白藜芦醇对HepG2细胞增殖及自噬的调节作用及初步机制  

Regulation of Proliferation and Autophagy and Its Possible Mechanisms of Resveratrol on HepG2 Cells in Hypoxia

作　　者：严俊[1] 李晓姝[2] 孙慧燕[1] 王华[1] 肖凤君[1] 李庆芳[1] 杨月峰[1] 王立生[1] 吴祖泽[1] 

机构地区：[1]军事医学科学院放射与辐射研究所,北京100850 [2]沈阳市第四人民医院,沈阳110031

出　　处：《中国科学：生命科学》2011年第6期456-461,共6页Scientia Sinica(Vitae)

基　　金：国家重点基础研究发展计划(批准号:2006CB504100);国家自然科学基金重点项目(批准号:30930041)资助

摘　　要：白藜芦醇(resveratrol)是天然存在于葡萄、红酒及花生等中的一种多酚类化合物,具有抗癌、抗氧化等作用.目前针对resveratrol抗癌作用的研究大多侧重于常氧状态,而对于更接近体内肿瘤生长环境即低氧状态的研究相对匮乏.本文以肝癌细胞HepG2为模型,探讨了低氧(1%O2)条件下resveratrol抑癌的相关功能和机制.结果表明,在低氧状态下resveratrol不仅抑制HepG2细胞的活性,而且也促进了低氧诱导的自噬保护机制;进一步研究发现,去乙酰化酶Sirt1和鞘氨醇激酶SPK1也参与上述过程.本文初步揭示了低氧状态下癌细胞对resveratrol敏感性低的可能机制,更加明确resveratrol在实体瘤中的抗癌作用,并为resveratrol的药物研发提供了借鉴.Resveratrol as a polyphenolic compound is naturally enriched in grapes, red wine and peanuts. Resveratrol has been reported to have potent anticancer and antioxidant properties. Most studies about the anti-cancer effect of resveratrol have been described previously when cells on the normoxia. The effect of resveratrol in hypoxia, the environment which mimics the state of tumor in vivo remains unclear. In this study, human hepatocellular carcinoma HepG2 cells were used to understand the effects and the possible mechanisms by which resveratrol acts as an anticancer agent in hypoxic conditions （1% 02）. Our data show that resveratrol significantly inhibits HepG2 cell viability in hypoxia, and promotes hypoxia stress induced autophagy as well. We also found that the NAD-dependent deacetylase （Sirtl） and sphingosine kinase 1 （SPK1） might be involved in the effects of resveratrol in hypoxia. Collectively, our studies reveal the possible mechanisms of insensitive effect of the resveratrol in hypoxia, and further clarify the anticancer effect of resveratrol on solid tumor cells, providing a reference for drug development of resveratrol.

关 键 词：白藜芦醇 肿瘤 自噬 去乙酰化酶 鞘氨醇激酶 

分 类 号：R285.5[医药卫生—中药学]