Dendrobium officinale polysaccharide Converts M2 into M1 Subtype Macrophage Polarization via the STAT6/PPAR-r and JAGGED1/NOTCH1 Signaling Pathways to Inhibit Gastric Cancer

Dendrobium officinale polysaccharide (DOP) has shown various biological activities. However, the ability of DOP to participate in immune regulation during anti-gastric Cancer treatment has remained unclear. In this study, the in vitro results showed that DOP has the potential to polarize THP-1 macrophages from the M2 to the M1 phenotype, downregulate the STAT6/PPAR-r signaling pathway and the protein expression of their down-targeted ARG1 and TGM2, and further decrease the main protein and mRNA expression in the JAGGED1/NOTCH1 signaling pathway. DOP suppressed the migration of gastric Cancer cells by decreasing the protein expression of N-Cadherin and Vimentin and increasing E-cadherin. In addition, CM-DOP promoted the Apoptosis of gastric Cancer cells by upregulating Caspase-3 and increasing the ratio of Bax/Bcl-2. In vivo, DOP effectively inhibited the growth of tumors and the expression of Ki-67. In summary, these findings demonstrated that DOP converted the polarization of M2 subtype macrophages into M1 subtypes via the STAT6/PPAR-r and JAGGED1/NOTCH1 signaling pathways in order to reduce Apoptosis and prevent migration, thus indicating the potential of DOP as an Adjuvant tumor therapy in preclinical and clinical trials.

Dendrobium officinale polysaccharide (DOP); JAGGED1/NOTCH1 signaling pathway; STAT6/PPAR-r signaling pathway; gastric cancer; macrophage polarization.