复方黄芪口服液联合化疗药物抗肿瘤效应机制研究

The study on mechanism of the anti-tumor effect of Fufang Huangqi Oral Solution combined chemotherapy

[目的]研究复方黄芪口服液联合化疗药物抗肿瘤效应及作用机制,为复方黄芪口服液抗肿瘤免疫疗法和临床应用提供依据。[方法]构建H22荷瘤小鼠模型,随机分为荷瘤模型组、复方黄芪口服液组、环磷酰胺组和联合用药组。给药16 d后,分离肿瘤组织,评价抗肿瘤效应;血细胞分析仪测定外周血白细胞、中性粒细胞和单核细胞数量;四甲基偶氮唑蓝(MTT)法检测荷瘤小鼠淋巴细胞增殖功能;流式细胞术检测脾淋巴细胞Ⅰ型辅助性T细胞(CD4^(+)IFN-γ^(+)T细胞)和调节性T细胞(CD4^(+)Foxp3^(+)Treg细胞)表达水平。[结果]与单用环磷酰胺相比,复方黄芪口服液联合环磷酰胺对肿瘤抑制率无明显影响,能够显著提高荷瘤小鼠脾淋巴细胞的增殖能力,差异有统计学意义(P<0.01);复方黄芪口服液联合环磷酰胺进行干预后,可增加白细胞和中性粒细胞数量(P<0.01或P<0.05),上调CD4^(+)IFN-γ^(+)T细胞比例,下调具有免疫抑制作用的CD4^(+)Foxp3^(+)Treg细胞表达。[结论]复方黄芪口服液联合化疗药物具有显著抗肿瘤免疫效应,其机制可能与促进Th1细胞反应和下调Treg细胞表达,从而提高机体的抗肿瘤免疫功能有关。

[Objective]This paper was designed to investigatethe anti-tumor effect of Fufang Huangqi Oral Solution(FFHQKY)combined chemotherapyin H22 tumor-bearing mice and reveal its mechanism.This study will provided a basis for the theoretical foundation of antitumor immunotherapy of FFHQKY.[Methods]The H22 tumor-bearing mice were established to investigate the effect ofanti-tumor immunological effect of FFHQKY combined chemotherapy.Mice were divided into four groups,including model group,FFHQKY treated-group,cyclophosphamide(CTX)group,and combination treated group.After 16 days of intragastric administration,the tumor tissue were isolated to assess the anti-tumor effect of FFHQKY,the lymphocyte cells proliferation was detected by MTT method,the total cell numbers of leukocyte,monocyte,neutrophil were measured by hematology analyzer.The expression of Treg(CD4^(+)Foxp3^(+))and Th1 cells(CD4^(+)IFN-γ^(+))were detected by flow cytometry.[Results]Compared with CTX group,the combination treated group had no influence on inhibitory rate of tumor but significantly recovered the lymphocyte proliferation activity from H22 tumor-bearing mice in response to ConA,increased the cells count of leukocyte and neutrophil.Importantly,compared with CTX group,the percent of Th1 cellsTh1 cells(CD4^(+)IFN-γ^(+))were increased in combination treated group.Furthermore,combination treatment reduced the expression of Treg(CD4^(+)Foxp3^(+)).[Conclusion]Combination FFHQKY with chemotherapy exerted significantly anti-tumor immunological,the mechanism of action may be linked to activate Th1 cells response and down-regulated Treg expression,consequently enhance anti-tumor immunological effect.