Dendrobium huoshanense polysaccharide inhibits NSCLC proliferation and immune evasion via FXR1-IL-35 axis signaling pathway.

Dendrobium huoshanense has received special attention for its advantages in the treatment of lung cancer, but the underlying molecular mechanisms are not yet well understood. First, we obtained 8 active ingredients and 159 effective action targets of Dendrobium huoshanense using network pharmacology, and searching target interactions through STRING, constructing the PPI network and KEGG, GO and Hallmark enrichment analysis. Then, we combined target's enrichment analysis and GSEA enrichment analysis of IL-35, indicating the mechanism of cDHPs for non-small cell lung cancer (NSCLC) may be related to tight junction and NSCLC pathway. Further, FXR1 and ACTR3 were identified as core therapeutic targets, and high expression of FXR1 or ACTR3 was significantly associated with poor prognosis of patients. The analysis of single-cell data also indicated that the percentage of CD4-CTLA4-Treg cells may be increased by the expression of IL-35, resulting in a suppressive immune microenvironment. Next, In vivo experiment, we detected iTr35 by flow cytometry, detected IL-35 level by RT-PCR, Western blotting and ELISA, and detected NK cell activity to explore the immunomodulatory effects and anti-tumor mechanism of cDHPs. After cDHPs administration, the conversion of CD4