富含总三萜的灵芝提取物抑制小鼠MC38结肠癌皮下移植瘤增殖的研究OA

Objective:To investigate effects of Ganoderma lucidum extract rich in total triterpenes on inhibition of subcutane-ous colon cancer in mice with MC38 cell line,and analyze its impact on changes in myeloid-derived suppressor cells(MDSCs)and T cells.Methods:Initially,potential targets of Ganoderma lucidum reported in literature were predicted using databases such as Swiss TargetPrediction and TCMSP,and potential targets of colon cancer were inferred by combining disease targets related to colon cancer retrieved from GeneCards database;STRING database was utilized to construct a protein-protein interaction(PPI)network for inter-secting targets;Cytoscape software was employed for network topology analysis of targets selected from STRING database to identify key targets and speculate on potential active drug components;DAVID database was used to perform GO and KEGG pathway enrich-ment analysis on differential genes.Based on results of inferred potential important active components of Ganoderma lucidum in inhibiting tumor growth,a subcutaneous colon cancer mouse model with MC38 cell line was established and administered intragastric treatment with Ganoderma lucidum extracts of varying total triterpene content.Ki67 immunohistochemical staining was used to observe prolifera-tive capacity of mouse tumors;flow cytometry was used to determine changes in T cells and MDSCs in tumors and spleens of mice;ELISA was used to measure level of IL-6 in mouse serum.Results:Network pharmacology analysis revealed that main active compo-nents in Ganoderma lucidum extract that inhibit colon cancer belong to class of total triterpenes.Mice bearing tumors were adminis-tered intragastric treatments with N(normal saline),Formulation A(0.01%total triterpenes),Formulation B(0.2%total triterpenes)and Formulation C(3.5%total triterpenes).Compared to N group,growth of tumors in colon cancer mice treated with Formulation C was significantly slowed,and tumor volume was markedly reduced.ELISA results demonstrated that Formulation C could decrease expression of IL-6 in mouse serum.Flow cytometry results showed that proportion of G-MDSCs in tumors and spleens of mice in Group C was decreased,while proportion of CD8+T cells was increased.Conclusion:Ganoderma lucidum extract rich in total triterpenes can significantly inhibit growth of colon cancer in MC38 cell line subcutaneous mouse model,markedly down-regulate proportion of G-MDSCs in tumors and spleens of tumor-bearing mice,and increase proportion of CD8+T cells,suggesting that inhibitory effect of Ganoderma lucidum extract rich in total triterpenes on colon cancer is mainly achieved through modulation of immune responses.