Exploration of Dendrobium officinale polysaccharide (DOP)'s potential targeted therapy in T-ALL combining network pharmacology, bioinformatics and experimental validation.

Dendrobium officinale polysaccharide (DOP) has been shown to produce significant antitumor activities, but its effect on T-cell acute lymphoblastic leukemia (T-ALL) remains elusive. Herein were confirmed that DOP contains six major glycosidic bonds with pharmacological activities. We explored the therapeutic targets and mechanisms of DOP using network pharmacology, bioinformatics analysis and experimental validation. By analyzing the data from publicly available databases and RNA Sequencing (RNA-Seq) profiles of DOP-treated Jurkat cells, we identified 13 common targets shared by DOP and T-ALL. Using STRING for protein-protein interaction network construction and CytoHuba for target identification, 13 hub targets including CARD11 and CCND1 were identified. GO and KEGG pathway analyses showed that these hub targets were involved in regulation of cell apoptosis and proliferation through the key pathways related to cancer, cell cycle, PI3K-AKT, and NF-κB signaling. The clinical relevance of these targets was verified by UALCAN and GEPIA2. Molecular docking analyses indicated significant interactions between glycosidic structures of DOP and the key targets. Experimental validation with Jurkat cells demonstrated that DOP treatment induced cell cycle arrest in S phase, increased cell apoptosis rates compared to cytosine, and caused changes in expression levels of 13 genes, which supported the antitumor effects of DOP against T-ALL. These findings revealed the molecular mechanism of DOP against T-ALL and highlight its multifaceted role in targeting diverse therapeutic pathways.