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OA
Nrf2 promotes the proliferation of nasopharyngeal carcinoma cells by mediating M2 polarization of macrophages through regulation of NOX2/SYK/SHP2 pathway
目的:本研究旨在探讨鼻咽癌中核因子(红细胞衍生2)相关因子2(Nrf2)通过调控肿瘤相关巨噬细胞内NADPH氧化酶2(NOX2)/脾酪氨酸激酶(SYK)/含Src同源2结构域蛋白酪氨酸磷酸酶2(SHP2)信号轴,导致M2极化,并促进鼻咽癌肿瘤增殖的分子机制.方法:选择GEO数据库中GSE12452数据集进行生物信息学分析,以探讨Nrf2的表达水平对鼻咽癌进展的影响.选择THP-1细胞进行分析,使用佛波酯12-肉豆蔻酸酯对THP-1进行诱导,将经过诱导后的巨噬细胞分为对照组、Nrf2-KD组,Nrf2-KD+SYK抑制剂,Nrf2+SHP2激动剂组,使用免疫印迹检测Nrf2、NOX2、SYK、SHP2蛋白的表达;采用qPCR检测M1、M2标志物的表达;通过Transwell实验评估细胞增殖和迁移侵袭能力.结果:与对照组相比,Nrf2-KD组Nrf2、SHP2蛋白表达下降,NOX2、SYK蛋白表达上升.与Nrf2-KD组 相 比,Nrf2-KD+SYK抑制剂组NOX2和SYK蛋白表达下降,SHP2蛋白表达上升.与对照组相比,Nrf2-KD组M1标志物白细胞介素(IL)-1β、肿瘤坏死因子α(TNFα)、IL-8的mRNA表达上调,M2标志物Arginase-1、CD206、YM-1的mRNA表达下调;与Nrf2-KD组相比,使用SYK抑制剂后M1标志物表达下降,M2标志物升高.与对照组相比,Nrf2-KD组细胞增殖和侵袭能力降低;与Nrf2-KD组相比,Nrf2-KD+SYK抑制剂细胞增殖和侵袭能力升高,而使用SHP2激动剂处理后,细胞增殖和侵袭能力得到逆转.结论:鼻咽癌中Nrf2通过调控肿瘤相关巨噬细胞中的NOX2/SYK/SHP2信号轴促进M2极化,从而增强鼻咽癌细胞增殖和侵袭能力.
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.
杨良才;罗晴;刘定荣;廖兴春;周鑫
内江市第二人民医院 耳鼻咽喉头颈外科,内江 641000内江市第二人民医院 病理科,内江 641000内江市第二人民医院 耳鼻咽喉头颈外科,内江 641000内江市第二人民医院 耳鼻咽喉头颈外科,内江 641000内江市第二人民医院 耳鼻咽喉头颈外科,内江 641000
医药卫生
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2
nasopharyngeal carcinomanuclear factor erythroid 2-related factor 2NADPH oxidase 2spleen tyrosine kinaseSrc homology 2 domain-containing protein tyrosine phosphatase 2
《解剖学杂志》 2026 (4)
350-354,415,中插1,7
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