敲除Nrf2对4NQO诱导的小鼠舌癌变过程中增殖与分化的影响  

Effect of Nrf2 knockout on proliferation and differentiation in a 4NQO-induced mouse oral carcinogenesis model

作　　者：文金林 宿颖[1] 孙正[2] 张辛燕[1] WEN Jin-lin;SU Ying;SUN Zheng;ZHANG Xin-yan(Beijing Institute of Dental Research,Capital Medical University School of Stomatology,Beijing 100050,China)

机构地区：[1]首都医科大学口腔医学院口腔医学研究所,北京100050 [2]首都医科大学口腔医学院黏膜科,北京100050

出　　处：《北京口腔医学》2023年第6期381-384,共4页Beijing Journal of Stomatology

基　　金：北京市自然科学基金(7202057);国家自然科学基金(81772868)。

摘　　要：目的研究核因子E2相关因子(Nrf2)在4-硝基喹啉-1-氧化物(4NQO)诱导的小鼠舌癌发生中对增殖和分化的影响。方法野生型(WT)与Nrf2基因敲除(Nrf2-/-)C57BL/6J小鼠各36只,其中阴性对照组10只,饮用纯净水,4NQO组26只,饮用4NQO水溶液(50μg/ml)16周。24周末处死小鼠,取舌组织用于病理学分析、Brdu和免疫组化(IHC)染色。通过生物信息学分析Nrf2与KLF4的相关性。结果构建了4NQO诱导的小鼠舌癌模型,并发现Nrf2-/-小鼠的舌癌发生率和Brdu染色的阳性细胞数明显高于WT小鼠。IHC染色显示,Nrf2-/-小鼠舌组织中分化相关基因KLF4、Loricrin、CK5的表达显著低于WT小鼠。在舌癌和正常组织中Nrf2的表达与KLF4成显著正相关。结论敲除Nrf2可以促进舌癌发生和细胞增殖,并抑制癌变过程中的细胞分化。Objective To study the effect of nuclear factor erythroid 2-related factor 2(Nrf2)on proliferation and differentiation in a 4-nitroquinoline-1-oxide(4NQO)-induced mouse oral carcinogenesis model.Methods Thirty-six wildtype(WT)and thirty-six Nrf2 gene knockout(Nrf2-/-)C57BL/6J mice were divided into the negative control group treated with pure water and the 4NQO group treated with 4NQO solution(50μg/ml)for 16 weeks,respectively.After the mice were sacrificed at the end of 24 weeks,the tongue tissues were taken for pathological analysis,Brdu and immunohistochemical(IHC)staining.A correlation analysis between the expression of Nrf2 and KLF4 was performed by bioinformatic methods.Results A 4NQO-induced mouse tongue cancer model was established and the incidence of tongue cancer and the number of Brdu-stained positive cells were significantly increased in Nrf2-/-mice compared with that in WT mice.IHC results showed that the expression of differentiation-related genes KLF4,Loricrin and CK5 was decreased in the tongue tissues of Nrf2-/-mice compared with WT mice.In addition,the Nrf2 expression was positively correlated with KLF4 expression in tongue cancer and normal tissues.Conclusions Knockout of Nrf2 can promote the tongue carcinogenesis and cell proliferation and inhibit the cell differentiation during carcinogenesis.

关 键 词：NRF2 舌癌 增殖 分化 

分 类 号：R739.2[医药卫生—肿瘤]