Nrf2调控自噬对于宫颈癌发生发展的作用及机制研究  

Regulatory effect of Nrf2 on autophagy in the development of cervical cancer

作　　者：李晓兰[1] 赵骏达 马俊旗[1] LI Xiaolan;ZHAO Junda;MA Junqi(Department of Obstetrics and Gynecology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi Xinjiang 830054,China)

机构地区：[1]新疆医科大学第一附属医院妇产科,新疆乌鲁木齐830054

出　　处：《转化医学杂志》2020年第6期335-339,共5页Translational Medicine Journal

基　　金：新疆维吾尔自治区自然基金项目(2015211C059)。

摘　　要：目的研究宫颈癌组织中核因子E2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)及细胞自噬人蛋白的表达情况,探讨Nrf2调控自噬对宫颈癌发生发展的作用机制。方法收集2018年1月-12月在新疆医科大学第一附属医院妇产科就诊的50例宫颈癌标本及癌旁组织,免疫组化检测组织标本中Beclin1、LC3、p62、Nrf2的表达情况;在宫颈癌SiHa细胞株内分别转染Nrf2 siRNA及p62 siRNA后,Western Blot检测Nrf2、p62、Bcl2、Bax蛋白表达情况,MTT检测细胞增殖情况。结果免疫组化结果显示Beclin1、LC3在宫颈癌组织内显著低表达,分别为18.0%(9/50)和20.0%(10/50),而p62和Nrf2在宫颈癌组织内显著高表达,分别为78.0%(39/50)和86.0%(43/50),差异有统计学意义(P<0.05)。分别在宫颈癌SiHa细胞株内转染Nrf2 siRNA及p62 siRNA后,细胞内Nrf2与p62表达呈正相关,且均能显著促进细胞凋亡,差异有统计学意义(P<0.05)。细胞增殖在Nrf2 siRNA和p62 siRNA组显著降低,差异有统计学意义(P<0.05)。结论宫颈癌细胞内,Nrf2与p62存在环形正向调控作用,且抑制Nrf2和p62的表达后可以显著促进细胞凋亡,抑制细胞增殖。Objective To study the expression of nuclear factor-erythroid 2-related factor 2(Nrf2)and autophagy proteins in cervical cancer tissues,and to explore the regulation of Nrf2 on autophagy in the development of cervical cancer.Methods 50 cases of cervical cancer specimens and adjacent tissues were obtained from Department of obstetrics and gynecology,the First Affiliated Hospital of Xinjiang Medical University from January 2018 to December.The expression of Beclin1,LC3,p62 and Nrf2 in immunohistochemicaltissues was detected.In cervical cancer cell line SiHa,Nrf2 siRNA and p62 siRNA were transfected into cells,and the expression of Nrf2,p62,Bcl2 and Bax proteins were detected by western blot.Cell proliferation was detected by MTT.Results The results of immunohistochemistry showed that the expression of Beclin1、LC3 in cervical carcinoma was significantly lower than that in cervical cancer tissues,which were 18.0%(9/50)and 20.0%(10/50),respectively.The expression of p62 and Nrf2 was significantly higher in cervical cancer tissues,respectively.The difference was statistically significant(P<0.05)for 78.0%(39/50)and 86.0%(43/50).After transfection of Nrf2 siRNA and p62 siRNA in cervical cancer SiHa cell line,Nrf2 was positively correlated with p62 expression,and both of them could significantly promote apoptosis,the difference was statistically significant(P<0.05).Cell proliferation was significantly decreased in the Nrf2 siRNA and p62 siRNA groups,and the difference was statistically significant(P<0.05).Conclusion Nrf2 and p62 have positive circular regulation in cervical cancer cells,and inhibition of Nrf2 and p62 expression can significantly promote apoptosis and inhibit cell proliferation.

关 键 词：宫颈癌 核因子E2相关因子2 自噬 p62蛋白 细胞增殖与凋亡 

分 类 号：R737.33[医药卫生—肿瘤]