Parthenolide inhibits the malignant progression of gallbladder cancer cells by regulating CCL2-mediated phenotypic polarization of tumor-associated macrophages
10.19405/j.cnki.issn1000-1492.2025.12.002
- VernacularTitle: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
- Author:
Hongchen Li
1
;
Halimulati Wubulikasimu
1
;
Jun Chen
1
Author Information
1. Dept of General Surgery, Afiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University, Urumqi 830000
- Publication Type:Journal Article
- Keywords:
gallbladder cancer;
parthenolide;
tumor-associated macrophage;
CC chemokine ligand 2;
proliferation;
migration;
invasion
- From:
Acta Universitatis Medicinalis Anhui
2025;60(12):2197-2206
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role and molecular mechanism of parthenolide(PTL) in regulating tumor-associated 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, migration and invasion, respectively.
Results:Compared with the TAM group, the TAM+PTL group showed increased 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 decreased, cell proliferation activity, colony formation, migration and invasion were all reduced (P < 0. 05) . Compared with the TAM + PTL group , the TAM + PTL + OE-CCL2 group showed decreased CD86 expression and increased 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 downregulating CCL2 expression in gallbladder cancer cells , thereby preventing the proliferation , migration and invasion of gallbladder cancer cells.
- Full text:2026030223110955367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_李鸿晨.pdf
