中药新药与临床药理2026，Vol.37Issue(3)：413-423,11.DOI:10.19378/j.issn.1003-9783.2026.03.004
补地参连方抑制JAK/STAT通路调控肿瘤相关巨噬细胞极化抗结直肠癌的机制
Mechanistic Study on Budishenlian Formula Inhibiting Colorectal Cancer by Regulating Tumor-Associated Macrophage Polarization via Suppression of the JAK/STAT Pathway
摘要
Abstract
Objective To investigate the mechanism of Budishenlian Formula(mainly composed of Psoraleae Fructus,Rehmanniae Radix,Ginseng Radix et Rhizoma,Coptidis Rhizoma,etc.)in inhibiting colorectal cancer by regulating tumor-associated macrophages(TAMs)polarization through suppression of the Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway.Methods Forty-two BALB/c mice were randomly divided into a blank control group,a model group,a 5-fluorouracil(5-FU,0.025 g·kg-1)group,and low-,medium-,and high-dose Budishenlian Formula groups(10.98,21.97,43.94 g·kg-1),with 7 mice per group.The inhibitory effect of Budishenlian Formula on mouse subcutaneous xenograft tumors was assessed by observing body mass,tumor volume,liver and kidney indices,and hematoxylin-eosin(HE)staining.Flow cytometry was used to detect markers of M1 and M2 type TAMs in tumor tissue.Enzyme-linked immunosorbent assay(ELISA)was performed to measure serum and tissue levels of TAM-related inflammatory factors,including interleukin(IL)-1β,IL-6,and transforming growth factor-β(TGF-β).Immunohistochemical staining was used to detect the expression of p-JAK2 and p-STAT3 proteins in mouse tumor tissue.Western Blot analysis was conducted to detect changes in protein expression levels of cluster of differentiation 86(CD86),mannose receptor(CD206),p-JAK2/JAK2,and p-STAT3/STAT3 in mouse tumor tissue after Budishenlian Formula intervention.Real-time quantitative polymerase chain reaction(qPCR)was used to measure the mRNA expression levels of CD86,CD206,JAK2,and STAT3 in tumor tissue.Results Compared with the model group,Budishenlian Formula inhibited the growth of subcutaneous xenograft tumors(P＜0.05,P＜0.01,P＜0.001),increased the degree of necrosis in tumor tissue,and reduced pathological mitotic figures.Compared with the blank control group,serum levels of IL-6 and IL-1β were significantly decreased(P＜0.001,P＜0.000 1),while TGF-β levels were significantly increased(P＜0.000 1)in the model group.Compared with the model group,both the 5-FU group and the Budishenlian Formula dose groups showed significantly increased levels of IL-6 and IL-1β(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1)and significantly decreased levels of TGF-β(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1)in serum and tumor tissue.Compared with the model group,the treatment groups showed increased protein and mRNA expression of CD86(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1),and decreased protein and mRNA expression of CD206,p-JAK2,JAK2,p-STAT3,and STAT3(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1)in tumor tissue.Conclusion Budishenlian Formula exhibits significant inhibitory effects on colorectal cancer and may influence the polarization of TAMs towards the M1 phenotype in colorectal cancer by regulating the JAK/STAT signaling pathway.关键词
补地参连方/结直肠癌/肿瘤相关巨噬细胞/JAK/STAT信号通路/温滋解毒法/小鼠Key words
Budishenlian Formula/colorectal cancer/tumor-associated macrophages/JAK/STAT signaling pathway/warming,nourishing,and detoxifying method/mice分类
医药卫生引用本文复制引用
唐明君,袁伟琛,陈海彬,周洪立,庄育培,梁雨薇,周红光,于修永..补地参连方抑制JAK/STAT通路调控肿瘤相关巨噬细胞极化抗结直肠癌的机制[J].中药新药与临床药理,2026,37(3):413-423,11.基金项目
国家自然科学基金面上项目(81973737) （81973737）
江苏省中医药科技发展项目重点项目(ZD202301) （ZD202301）
第二届全国名中医工作室建设项目(国中医药人教函[2022]245号) （国中医药人教函[2022]245号）
吴勉华全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号) （国中医药人教函[2022]75号）
吴勉华江苏省名老中医药专家传承工作室建设项目(苏中医科教[2021]7号) （苏中医科教[2021]7号）
江苏省研究生科研与实践创新计划项目(KYCX24_2247) （KYCX24_2247）
南京中医药大学自然科学基金项目(XZR2024167). （XZR2024167）
