中国肿瘤生物治疗杂志2026，Vol.33Issue(4)：373-378,6.DOI:10.3872/j.issn.1007-385x.2026.04.003
蟾毒灵通过抑制TAM介导的STAT3磷酸化降低结直肠癌细胞PD-L1表达
Bufalin reduces PD-L1 expression in colorectal cancer cells through suppressing TAM-mediated STAT3 phosphorylation
摘要
Abstract
Objective:To investigate the regulatory effect of bufalin(BU)on tumor-associated macrophage(TAM)-mediated programmed death-ligand 1(PD-L1)expression in colorectal cancer(CRC)cells and to elucidate the underlying molecular mechanism.Methods:An in vitro co-culture system was established using HCT116 cells and THP-1-derived macrophages.THP-1 cells were differentiated into M0 macrophages by PMA treatment and further stimulated with HCT116-conditioned medium(CM)to generate TAM-like cells.Flow cytometry was used to detect CD11b and CD206 expressions and assess macrophage polarization level.The changes in the expression levels of TGF-β,IL-10,STAT3/p-STAT3,and PD-L1 were detected by RT-qPCR and WB assay.A STAT3 knockdown cell line(HCT116sh-STAT3),constructed by lentiviral transduction,was combined with BU treatment to verify the role of the STAT3/PD-L1 signaling pathway.Results:HCT116-derived CM induced macrophage polarization toward the M2 phenotype,as evidenced by an increased proportion of CD11b⁺CD206⁺ cells(P<0.01)and elevated expression of TGF-β and IL-10(both P<0.001).TAM-conditioned medium significantly promoted STAT3 phosphorylation(P<0.001)and upregulated PD-L1 expression at both mRNA and protein levels in HCT116 cells(P<0.001 or P<0.01).BU treatment markedly suppressed TAM-mediated STAT3 phosphorylation and concomitantly reduced PD-L1 expression(both P<0.01).STAT3 knockdown decreased PD-L1 expression,showing a similar trend to BU treatment.Conclusion:BU downregulates PD-L1 expression in CRC cells by inhibiting TAM-mediated STAT3 signal activation,suggesting its potential application value in regulating the tumor immune microenvironment.关键词
结直肠癌/肿瘤相关巨噬细胞/程序性死亡配体1/HCT116细胞Key words
colorectal cancer(CRC)/tumor-associated macrophage(TAM)/programmed death-ligand 1(PD-L1)/HCT116 cell分类
医药卫生引用本文复制引用
路畅,尚靖,陈进宝,朱媛,钟佳妮,殷佩浩..蟾毒灵通过抑制TAM介导的STAT3磷酸化降低结直肠癌细胞PD-L1表达[J].中国肿瘤生物治疗杂志,2026,33(4):373-378,6.基金项目
上海市卫生健康系统重点学科(2024ZDXK0044,2024ZDXK0046) （2024ZDXK0044,2024ZDXK0046）
上海市普陀区卫生健康系统科技创新项目(ptkwws202409) （ptkwws202409）
上海市第六人民医院联合共建科学研究基金(23-LY-03) （23-LY-03）
安徽医科大学研究生科研与实践创新项目(YJS20240117) （YJS20240117）
