解剖学杂志2026，Vol.49Issue(4)：350-354,415,中插1,7.DOI:10.3969/j.issn.1001-1633.2026.04.007
核因子相关因子2通过调控NOX2/SYK/SHP2通路介导的巨噬细胞M2极化进而促进鼻咽癌细胞增殖
Nrf2 promotes the proliferation of nasopharyngeal carcinoma cells by mediating M2 polarization of macrophages through regulation of NOX2/SYK/SHP2 pathway
杨良才 1罗晴 2刘定荣 1廖兴春 1周鑫1
作者信息
- 1. 内江市第二人民医院 耳鼻咽喉头颈外科,内江 641000
- 2. 内江市第二人民医院 病理科,内江 641000
- 折叠
摘要
Abstract
Objective:To investigate the molecular mechanisms by which nuclear factor erythroid 2-related factor 2(Nrf2),highly expressed in nasopharyngeal carcinoma(NPC),leads to M2 polarization and promotes tumor proliferation in NPC by regulating the Nrf2/NADPH oxidase 2(NOX2)/spleen tyrosine kinase(SYK)/Src homology 2 domain-containing protein tyrosine phosphatase 2(SHP2)signaling pathway in tumor-associated macrophages(TAMs).Methods:The GSE12452 dataset from the GEO database was selected for bioinformatics analysis to investigate the effect of Nrf2 expression level on NPC progression.THP-1 cells were selected for analysis and induced with PMA to differentiate into macrophages.The induced macrophages were divided into the following groups:control(NC group),Nrf2-knockdown(Nrf2-KD),Nrf2-KD+SYK inhibitor,and Nrf2+SHP2 agonist groups.Nrf2,NOX2,SYK,and SHP2 protein expression levels were detected by Western blotting.q-PCR was performed to detect the mRNA expression of M1 and M2 markers.Cell proliferation,migration,and invasion abilities were assessed by Transwell assays.Results:Nrf2 and SHP2 protein expression decreased and NOX2 and SYK protein expression increased in the Nrf2-KD group compared with the NC group.Compared with the Nrf2-KD group,NOX2 and SYK protein expression decreased and SHP2 protein expression increased in the Nrf2-KD+SYK inhibitor group.Compared with the NC group,the mRNA expression of the M1 markers(IL-1β,TNFα,and IL-8)was up-regulated,and the mRNA expression of the M2 markers(Arginase-1,CD206,and YM-1)was down-regulated in the Nrf2-KD group.Administration of a SYK inhibitor reversed this effect,decreasing M1 markers and increasing M2 markers compared to the Nrf2-KD group.Knockdown of Nrf2 reduced cell proliferation and invasion capabilities,compared to the NC group.However,the addition of a SYK inhibitor enhanced proliferation and invasion,which was reversed by an SHP2 agonist.Conclusion:Nrf2 in NPC promotes M2 polarization of TAMs by regulating the NOX2/SYK/SHP2 signaling pathway in TAMs,thereby enhancing the proliferation and invasion abilities of NPC cells.关键词
鼻咽癌/核因子(红细胞衍生2)相关因子2/细胞内NADPH氧化酶2/脾酪氨酸激酶/含Src同源2结构域蛋白酪氨酸磷酸酶2Key words
nasopharyngeal carcinoma/nuclear factor erythroid 2-related factor 2/NADPH oxidase 2/spleen tyrosine kinase/Src homology 2 domain-containing protein tyrosine phosphatase 2分类
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杨良才,罗晴,刘定荣,廖兴春,周鑫..核因子相关因子2通过调控NOX2/SYK/SHP2通路介导的巨噬细胞M2极化进而促进鼻咽癌细胞增殖[J].解剖学杂志,2026,49(4):350-354,415,中插1,7.
