木瓜总黄酮抗肿瘤活性研究

目的:研究木瓜总黄酮抗肿瘤活性。方法:通过乙醇-正丁醇萃取方法提取木瓜总黄酮;通过分子药物筛选模型、酶联免疫法检测木瓜总黄酮对免疫共刺激分子程序性死亡因子(PD)-1与其配体(PD-L1)结合的抑制作用。通过H22肿瘤细胞模型小鼠,观察木瓜总黄酮对模型小鼠体内肿瘤体积与存活时间的影响;流式细胞仪测定小鼠腹水中肿瘤细胞及淋巴细胞表面相关分子的表达。结果:正丁醇馏分中木瓜总黄酮占85%。木瓜总黄酮具有抑制PD-1和PD-L1结合的作用,且抑制效率具有剂量依赖性。木瓜总黄酮在复制模型10 d后对模型小鼠体内肿瘤有明显抑制作用;对S180细胞表面PD-L1表达具有明显抑制作用,对体内淋巴细胞侵润有明显增强作用。结论:木瓜总黄酮可以抑制PD-1与PD-L1的结合,同时可降低肿瘤细胞表面PD-L1的表达从而促进机体对肿瘤的免疫应答,最终达到抑制肿瘤生长,提高肿瘤鼠存活率的作用。

Study on Anti-tumor Activity Total Flavonoids from Chaenomeles speciosa

OBJECTIVE： To study anti-tumor activity of total flavonoids from Chaenomeles speciosa. METHODS ： Total flavonoids was extracted from C. speciosa with ethanol-n-butyl alcohol extraction method; by using molecular medicine selection model, ELISA assay was used to detect inhibitory effects of C. speciosa total flavonoids on the combination of PD-1 and PD-L1. The influence of C. speciosa on tumor volume and survival time in H22 tumor cell model mice were observed. Flow cytometry was adopted to detect the expression of associated molecules of tumor cell or lymphocyte＇ s surface which obtained from ascites of experimental mice. RESULTS： C. speciosa total flavonoids accounted for 85% in n-butyl alcohol fraction. C. speciosa total flavonoids could inhibit the combination of PD-1 and PD-L1, in dose-dependant manner. C. speciosa total flavonoids significantly inhibited tumor of model mice in vivolO d after modeling; C. speciosa total flavonoids significantly inhibited the expression of PD-L1 in S180 cell surface, while enhanced lymphocyte infiltration. CONCLUSIONS ： C. speciosa total flavonoids can inhibit the growth of tumor and improve survival rate of tumor bearing mice by inhibiting the combination of PD-1 and PD-L1 and reducing the expression of PD-L1 so as to promote immune response.