白藜芦醇通过诱导细胞自噬性死亡抑制宫颈癌的研究  

Resveratrol induces autophagic death of cervical cancer cells to exert antitumor effect

作　　者：孙晓东 周珍[1] 曾炼 谢丽霞 杜凯丽 桑明 SUN Xiao-dong;ZHOU Zhen;ZENG Lian;XIE Li-xia;DU Kai-li;SANG Ming(Xiangyang No.1 People’s Hospital,Hubei University of Medicine,Xiangyang 441000,China;Hubei Key Laboratory of Wudang Local Chinese Medicine Research,Hubei University of Medicine,Shiyan 442000,China)

机构地区：[1]湖北医药学院附属襄阳市第一人民医院,襄阳441000 [2]湖北医药学院武当特色中药研究湖北省重点实验室,十堰442000

出　　处：《天然产物研究与开发》2021年第2期208-215,共8页Natural Product Research and Development

基　　金：国家自然科学基金(81903005);湖北省实验动物资源开发及利用专项(2020DFE025);湖北省对外科技合作项目(2019AHB068);湖北医药学院药护学院团队项目(2017YHKT02)。

摘　　要：白藜芦醇作为一种广泛存在于药食同源植物中的非黄酮类多酚化合物,其抗肿瘤效果受到广泛关注,但在抑制宫颈癌方面仍缺乏体内效应的实验依据。本研究通过体内实验发现白藜芦醇具有明显的抗肿瘤生长作用,组织水平LC3B、P62和Beclin-1表达改变,推测白藜芦醇可能通过促进癌细胞的过度自噬抑制宫颈癌的进展;进一步通过体外细胞实验验证,发现白藜芦醇诱导自噬相关蛋白的表达,促进自噬小体和自噬溶酶体形成增多,分别与自噬激活剂雷帕霉素、自噬抑制剂巴伐洛霉素A1联用后检测细胞自噬流以及线粒体膜电位和细胞凋亡指标,发现白藜芦醇在自噬激活与自噬抑制的情况下可通过不同方式促进宫颈癌细胞的死亡。Resveratrol,a non-flavonoid polyphenol compound is widely present in Medicine and food homologous plants.Its anti-tumor effects have been widely recognized,but there is no experimental data reflecting the inhibition of cervical cancer in vivo.We found that resveratrol significantly inhibited tumor growth with upregulation of expression level of LC_(3)B and Beclin-1,while the expression level of P_(62) was downregulated.Thus,this suggests that resveratrol may inhibit the progress of cervical cancer by promoting excessive autophagy.Furthermore,resveratrol induced autophagy-related VMP1,Beclin-1,and LC3B protein expression and promoted the formation of autophagosomes and autophagolysosomes in vitro.Finally,it was found that resveratrol promoted excessive autophagy when combined with the activator rapamycin.It also promoted cell apoptosis when combined with the autophagy inhibitor bafilomycin A1.In conclusion,resveratrol exhibits inhibitory effects on cervical cancer during both autophagy activation and inhibition.

关 键 词：宫颈癌 白藜芦醇 细胞自噬 荷瘤模型 

分 类 号：R34[医药卫生—基础医学] Q291[生物学—细胞生物学]