阔叶十大功劳作用于FABP5介导免疫细胞干预肝癌的研究

Study on Effect of Kuoyeshidagonglao[Mahonia bealei(Fort.)Carr.]on FABP5 Mediated Immune Cells in Liver Cancer

目的探讨阔叶十大功劳(KYSDGL)通过介导免疫细胞干预肝癌的作用机制。方法通过网络药理学、分子对接和生物信息学等方法探索KYSDGL的活性成分以及靶点,并对肝癌数据集GSE45267、GSE89377进行挖掘,分析出KYSDGL通过介导免疫干预肝癌的作用机制,并加以实验验证。结果获得7个KYSDGL介导免疫细胞干预肝癌的靶点;分子对接显示其中有6个靶点(PTGS2、FABP5、ADRB2、AGTR1、ESR1、RORA)能与KYSDGL中的成分结合;且与对照组相比,肝癌组基因表达均具有显著差异性,和性别、癌症分期、淋巴结转移状况的临床指标具有很强的相关性;6个关键靶点的10年生存预后分析显示仅有FABP5及ESR1有预后价值;进一步免疫浸润分析结果显示,FABP5的表达水平与免疫细胞浸润有显著相关性;最后通过THPA数据库病理切片验证FABP5蛋白在人癌症组织中高表达,在对照组中低表达,我们通过Western blot实验也验证了与HepG2肝癌细胞组相比,KYSDGL含药血清组的FABP5蛋白表达下调(P<0.05)。结论KYSDGL可通过抑制FABP5的高表达而调控肿瘤免疫,从而达到干预肝癌的目的。

Objective To investigate the mechanism of action of Kuoyeshidagonglao[Mahonia bealei(Fort.)Carr.](KYSDGL)interfering with hepatocellular carcinoma through mediating the immune cells.Methods It explored the active components as well as targets of KYSDGL through network pharmacology,molecular docking and bioinformatics,and the data mining was carried on the liver cancer datasets GSE45267 and GSE89377 to analyze the mechanism of action of KYSDGL through mediating the immune microenvironment to intervene in liver cancer and verify it experimentally.Results Seven targets of KYSDGL-mediated immune cells intervention in cells were obtained.The molecular docking showed that six of them(PTGS2,FABP5,ADRB2,AGTR1,ESR1,RORA)could bind to components in KYSDGL.And all the gene expressions in the liver cancer group were significantly different compared with those in the control group,and there were strong correlations with clinical indicators of gender,cancer stage and lymph node metastasis status.The 10-year survival prognostic analysis of 6 key targets showed that only FABP5 and ESR1 had prognostic value.Further immune infiltration analysis showed that the expression level of FABP5 was significantly cor⁃related with immune cell infiltration.Finally,the pathological sections of THPA database verified that FABP5 protein was highly expressed in human cancer tissues and lowly expressed in control subjects.It also verified that FABP5 protein expression was down-regulated in KYSDGL-containing serum group compared with HepG2 hepatocellular carcinoma group by Western blot as⁃say(P<0.05).Conclusion KYSDGL can regulate the immunity of tumors by suppressing the high expression of FABP5 and thus intervene in liver cancer.