中国医科大学学报2025,Vol.54Issue(7):613-618,6.DOI:10.12007/j.issn.0258-4646.2025.07.007
敲低PTGS2抑制肿瘤相关巨噬细胞M2极化在鼻咽癌治疗中的应用价值
Effects of PTGS2 knockdown in nasopharyngeal carcinoma treatment by inhibiting tumor-associated macrophage M2 polarization
摘要
Abstract
Objective To investigate the effect of PTGS2 knockdown on tumor-associated macrophage(TAM)M2 polarization in the treatment of nasopharyngeal carcinoma(NPC).Methods Adenovirus-mediated knockdown of PTGS2 was performed in primary NPC cells.A co-culture system of primary NPC cells and TAMs and a mixed three-dimensional(3D)co-culture of primary NPC cells,TAMs,and human CD8+T cells were established in vitro.The control,Adv-PTGS2 shRNA,and Adv-shRNA NT groups were subjected to in vitro and in vivo experiments.In the co-culture system of primary NPC cells and TAMs,IL-12,IL-10,and TGF-βlevels in the culture superna-tants were determined using the ELISA.MMP-2 and MMP-9 expression levels in primary NPC were determined using Western blotting.In the mixed culture system of the three types of cells,cell viability was measured using the CCK-8 method.IFN-γand GZMBmRNA levels were determined using qPCR.The three types of cell-mixed cultures were injected subcutaneously into xenografts,and tumor growth was monitored for 21 d.Results Compared with control group,IL-12 levels increased and IL-10 and TGF-βlevels decreased in the culture supernatant of Adv-PTGS2 shRNA cells(P<0.05).MMP-2 and MMP-9 expression levels in primary NPC decreased(P<0.05).Com-pared with the control group,CD8+T cell proliferation ability and relative IFN-γand GZMBmRNA expression levels increased(P<0.05 for both experiments)in the Adv-PTGS2 shRNA cells.Compared with the control group,the Adv-PTGS2 shRNA group showed slower tumor growth(P<0.05)and lower tumor mass(P<0.05)in in vivo xenografts.Conclusion PTGS2knockdown inhibited TAM M2 pola-rization,regulated the immune-hot state in the tumor microenvironment,and inhibited NPC growth.关键词
鼻咽癌/肿瘤相关巨噬细胞/肿瘤微环境/CD8+T细胞/PTGS2Key words
nasopharyngeal carcinoma/tumor-associated macrophage/tumor microenvironment/CD8+T cell/PTGS2分类
医药卫生引用本文复制引用
姚晨,黄鑫,李钢,李增沛,李征..敲低PTGS2抑制肿瘤相关巨噬细胞M2极化在鼻咽癌治疗中的应用价值[J].中国医科大学学报,2025,54(7):613-618,6.基金项目
河南省科技发展计划(222102310135) (222102310135)