牡荆素通过调控巨噬细胞M2向M1极化发挥抗前列腺癌作用的机制  

Vitexin exerts anti-prostate cancer effects by modulating macrophage polari-zation from M2 to M1

作　　者：梁世佳 孙建明[1] 韩文均[1] 邵轶群 刘鹏[1] 王俊博 梁博闻 毛剑敏 LIANG Shijia;SUN Jianming;HAN Wenjun;SHAO Yiqun;LIU Peng;WANG Junbo;LIANG Bowen;MAO Jianmin(The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine,Shanghai 200137,China;Yueyang Hospital of Integrated Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属第七人民医院,上海200137 [2]上海中医药大学附属岳阳中西医结合医院,上海200437

出　　处：《中国免疫学杂志》2024年第12期2554-2558,2564,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金(82104720);浦东新区国家中医药发展综合改革试验区(PDZY-2021-0307);上海中医药大学附属第七人民医院人才培养计划(JCR2022-04)。

摘　　要：目的:探讨牡荆素调节巨噬细胞极化对前列腺癌小鼠肿瘤生长的影响。方法:采用C57BL/6J雄性小鼠构建RM-1前列腺癌荷瘤小鼠模型,随机分为模型组、牡荆素低、中、高剂量(40、80、160 mg/kg)组、阳性对照顺铂组,连续给药16 d后处死小鼠,称量肿瘤质量;HE染色观察肿瘤形态学变化;免疫组化检测Ki67的阳性率;流式细胞术检测肿瘤组织中巨噬细胞CD86^(+)CD11b、CD206^(+)CD11b表达;CCK8检测牡荆素对巨噬细胞RAW264.7的细胞毒作用,选取适合的牡荆素浓度;RT-qPCR检测M2型巨噬细胞标志物精氨酸酶(ARG-1)、Fizz1和Ym1 mRNA表达。结果:牡荆素体内抑制前列腺癌小鼠肿瘤体积和质量,诱导肿瘤组织坏死,抑制Ki67蛋白表达,增加小鼠肿瘤组织CD86^(+)CD11b^(+)M1型巨噬细胞表达,抑制CD206^(+)CD11b^(+)M2型巨噬细胞表达。10~20μmol/L牡荆素在体外对RAW264.7巨噬细胞无细胞毒性,且促进IL-4诱导的M2型巨噬细胞iNOS表达,抑制其CD206表达,同时抑制ARG-1、Fizz1和Ym1 mRNA表达。结论:牡荆素对前列腺癌小鼠肿瘤生长有较好的抑制作用,可能与将M2型巨噬细胞调节为M1型发挥免疫调节作用有关。Objective:To investigate effect of vitexin on macrophage polarization and its impact on tumor growth in a mouse model of prostate cancer.Methods:C57BL/6J male mice were used to establish RM-1 prostate cancer xenograft model.Mice were randomly divided into model group,vitexin-low,medium and high doses groups(40,80,160 mg/kg),and cisplatin group as positive control.After continuous administration for 16 days,mice were euthanized and tumor mass was measured.HE staining was performed to observe tumor morphology.Immunohistochemistry was used to detect Ki67 positive rate.Flow cytometry was conducted to measure expressions of CD86^(+)CD11b and CD206^(+)CD11b in tumor-associated macrophages.CCK8 assay was performed to assess cytotoxic effect of vitexin on RAW264.7 macrophages to determine suitable concentrations.RT-qPCR was used to measure mRNA expressions of M2 macrophage markers,including arginase-1(ARG-1),Fizz1 and Ym1.Results:Vitexin inhibited tumor volume and weight,induced tumor tissue necrosis,suppressed Ki67 protein expression,increased expression of CD86^(+)CD11b^(+)M1 macrophages,and inhibited CD206^(+)CD11b^(+)M2 macrophage expression in mouse tumor tissues in vivo.Vitexin at concentrations of 10~20μmol/L showed no cytotoxicity on RAW264.7 macrophages in vitro,and promoted expression of iNOS in IL-4-induced M2 macrophages while inhibiting CD206 expression,as well as suppressed mRNA expressions of ARG-1,Fizz1 and Ym1.Conclusion:Vitexin effectively inhibits tumor growth in a mouse model of prostate cancer,possibly by regulating M2 macrophages towards an M1 phenotype and exerting immunomodulatory effects.

关 键 词：前列腺癌 巨噬细胞 极化 牡荆素 

分 类 号：R284.2[医药卫生—中药学]