Suppression of stemness and enhancement of chemosensibility in the resistant melanoma were induced by Astragalus polysaccharide through PD-L1 downregulation.

ABSTRACT

Chemotherapy is commonly used in the clinical treatment of melanoma, but it is prone to resistance leading to the poor effectiveness. The mechanisms of resistance are complicated including the cancer stemness. Astragalus polysaccharide (APS) is one of the active components of traditional Chinese herbal medicine Astragalus Membranaceus. Our previous work was reported that APS had an inhibitory effect on the stemness of melanoma. In this study we established chemo-resistant melanoma cells and found that expression of stemness genes were upregulated in the resistant melanoma cells. And APS could downregulate expression of stemness genes. Furthermore, APS combined with cisplatin (DDP) could significantly slow down the tumor growth in the mouse model induced by DDP-resistant cells. In addition, we found that programmed death-ligand 1 (PD-L1) expression could be downregulated and the PI3K/AKT signaling could be affected by APS. These results suggested that APS could be a potential candidate in combination with chemotherapeutic agents, which might play a role in reducing the occurrence of resistance and improving the prognosis of melanoma patients.