Dendrobine Suppresses Tumor Growth by Regulating the PD-1/PD-L1 Checkpoint Pathway in Lung Cancer

Dendrobine is a bioactive alkaloid isolated from Dendrobium nobile. Studies have evaluated the anti-tumor effect of dendrobine in cancers, including lung cancer. However, the mechanism of dendrobine inhibiting tumors requires further study.

Bioinformatics was performed to screen the potential targets of dendrobine. The intersection of dendrobine and lung cancer targets was performed for KEGG analysis. CCK-8 was used to detect cell viability after dendrobine treatment. A xenograft mouse model was established to explore the effect of dendrobine on lung cancer. The percentages of PD-L1+, CD4+, CD8+, CD11b+, CD25+FOXP3+ cells, the expression of Ki-67 and caspase-3, the expression of pathway-related proteins, the levels of IL-2, IFN-γ, and TGF-β, and the changes of indicators of liver and renal function were measured.

Dendrobine regulated the PD1/PD-L1 checkpoint signaling pathway and affected the occurrence and development of lung cancer. Dendrobine decreased the cell viability of lung cancer. Dendrobine and anti-PD-L1 decreased tumor growth, increased caspase-3 expression, and reduced Ki-67 expression in tumor tissues. Dendrobine and anti-PD-L1 suppressed protein expression of PD-L1, p-JAK1/JAK1, and p-JAK2/JAK2 in tumor tissues. Greatly, dendrobine and anti-PD-L1 decreased the percentages of PD-L1+, CD11b+, and CD25+FOXP3+ cells, increased the percentages of CD4+ and CD8+cells, and enhanced the levels of IL-2, IFN-γ, and TGF-β in tumor tissues. Dendrobine demonstrated no hepatorenal toxicity to the tumor mice. The combination of dendrobine and anti-PD-L1 greatly strengthened the effects of dendrobine on tumors.

Dendrobine inhibited tumor immune escape by suppressing the PD-1/PD-L1 checkpoint pathway, thus restricting tumor growth of lung cancer.