安徽医科大学学报2025，Vol.60Issue(12)：2197-2206,10.DOI:10.19405/j.cnki.issn1000-1492.2025.12.002
小白菊内酯通过调控CCL2介导肿瘤相关巨噬细胞表型极化抑制胆囊癌细胞恶性进展
Parthenolide inhibits the malignant progression of gallbladder cancer cells by regulating CCL2-mediated phenotypic polarization of tumor-associated macrophages
摘要
Abstract
Objective To explore the role and molecular mechanism of parthenolide(PTL)in regulating tumor-as-sociated macrophage(TAM)polarization to inhibit the malignant progression of gallbladder cancer cells.Methods M0 macrophages were co-cultured with human gallbladder cancer cell line GBC-SD and treated with PTL,and the cells were divided into control group,TAM group,TAM+PTL group.Flow cytometry was used to determine the levels of CD86 and CD206 in macrophages.RT-qPCR and Western blot were used to determine the expressions of CD163,interleukin-10(IL-10)and arginase-1(Arg-1).ELISA and Western blot were used to determine the secretion of CC chemokine ligand 2(CCL2)in the supernatant of GBC-SD cells and the expression of CCL2 in the cells.GBC-SD cells were transfected with a CCL2 overexpression vector and divided into TAM,TAM+PTL,TAM+PTL+OE-NC,TAM+PTL+OE-CCL2 groups.Flow cytometry was used to assess CD86 and CD206 levels in macrophages,RT-qPCR and Western blot were used to assess CD163,IL-10 and Arg-1 expression.CCK-8 assay,plate-based colony formation assay and Transwell chamber assay were used to assess GBC-SD cell proliferation,mi-gration and invasion,respectively.Results Compared with the TAM group,the TAM+PTL group showed in-creased CD86 expression and decreased CD206 expression in macrophages,the mRNA and protein expressions of CD163,IL-10 and Arg-1 were downregulated,the CCL2 content and protein expression in GBC-SD cells de-creased,cell proliferation activity,colony formation,migration and invasion were all reduced(P＜0.05).Com-pared with the TAM+PTL group,the TAM+PTL+OE-CCL2 group showed decreased CD86 expression and in-creased CD206 expression in macrophages,the mRNA and protein expressions of CD163,IL-10 and Arg-1 were upregulated.Cell proliferation activity was enhanced,and colony formation,migration,and invasion all increased(P＜0.05).Conclusion Parthenolide inhibits the polarization of macrophages in TAM to M2 type by downregu-lating CCL2 expression in gallbladder cancer cells,thereby preventing the proliferation,migration and invasion of gallbladder cancer cells.关键词
胆囊癌/小白菊内酯/肿瘤相关巨噬细胞/CC类趋化因子配体2/增殖/迁移/侵袭Key words
gallbladder cancer/parthenolide/tumor-associated macrophage/CC chemokine ligand 2/prolifera-tion/migration/invasion分类
医药卫生引用本文复制引用
李鸿晨,哈力木拉提·吾布力卡斯木,陈骏..小白菊内酯通过调控CCL2介导肿瘤相关巨噬细胞表型极化抑制胆囊癌细胞恶性进展[J].安徽医科大学学报,2025,60(12):2197-2206,10.基金项目
新疆维吾尔自治区自然科学基金青年项目(编号:2021D01C240) Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2021D01C240) （编号:2021D01C240）
