Inhibition of M2-type macrophage-mediated migration and epithelial mesenchymal transition in colorectal cancer by bufalin
10.19405/j.cnki.issn1000-1492.2024.02.021
- VernacularTitle:蟾毒灵抑制M2型巨噬细胞介导的结直肠癌迁移和上皮间质转化
- Author:
Donghao TANG
1
,
2
,
3
;
Jinbao CHEN
;
Linlin JIA
;
Dongxiao SHEN
;
Jing SHANG
;
Yuejiao FENG
;
Jiahao LU
;
Zengyou XIAO
;
Yujie HE
;
Jie WANG
Author Information
1. 安徽医科大学上海普陀中心临床学院普外科,上海 200062
2. 安徽医科大学第五临床医学院,合肥 230032
3. 上海中医药大学附属普陀医院普外科,上海 200062
- Keywords:
bufalin;
M2 macrophage;
colorectal cancer
- From:
Acta Universitatis Medicinalis Anhui
2024;59(2):310-315
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of bufalin(BU)in inhibiting M2-type macrophage-mediated colorec-tal cancer metastasis.Methods Human acute leukemia mononuclear cells(THP-1)were differentiated into M0 macrophages using phorbol ester induction(PMA)for 48 hours.The M0 macrophages were then treated with IL-4 and IL-13 medium.Surface markers and morphological changes were observed through ELISA,morphology,and RT-qPCR experiments.RT-PCR and ELISA experiments were conducted to detect the surface markers TGF-β and IL-10 of M2 macrophages.The secretion level of IL-6 in the supernatant of M2 macrophages and colorectal cancer cells HCT116 was compared using ELISA.Additionally,the effect of conditioned medium on colorectal cancer cell HCT116 was assessed through Transwell,Wound healing,RT-qPCR,and Western blot experiments.Subsequent-ly,bufalin was added to the conditioned medium and the changes in AKT/PI3K protein,migration,and epithelial-mesenchymal transition ability in HCT116 were observed using Western blot,Transwell,Wound healing and RT-qPCR experiments.Results THP-1 were successfully differentiated into M2 macrophages.The activation of AKT/PI3K protein in HCT116 cells was induced by the secretion of IL-6 from M2 macrophages,which in turn promoted the migration and epithelial-mesenchymal transition ability of the HCT116 cells.The migration and epithelial-mes-enchymal transition mediated by M2 macrophages in HCT116 cells were effectively inhibited by Bufalin.Conclu-sion The release of IL-6 from M2 macrophages activates the AKT/PI3K signaling pathway in colorectal cancer cells,thereby promoting their migration and epithelial-mesenchymal transition capacity.Moreover,bufalin exhibits inhibitory effects on this effect.
