Effects of PTGS2 knockdown in nasopharyngeal carcinoma treatment by inhibiting tumor-associated macrophage M2 polarization
10.12007/j.issn.0258-4646.2025.07.007
- VernacularTitle: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
- Author:
Chen YAO
1
;
Xin HUANG
;
Gang LI
;
Zengpei LI
;
Zheng LI
Author Information
1. 南阳市第一人民医院耳鼻咽喉科二病区,河南 南阳 473000
- Publication Type:Journal Article
- Keywords:
nasopharyngeal carcinoma;
tumor-associated macrophage;
tumor microenvironment;
CD8+T cell;
PTGS2
- From:
Journal of China Medical University
2025;54(7):613-618
- CountryChina
- Language:Chinese
-
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.
