Astragalus polysaccharide enhances the antitumor efficacy of sunitinib in renal cell carcinoma by targeting the ZEB1-SCD1-Wnt/β-Catenin signaling pathway.

Renal cell carcinoma (RCC) is a highly prevalent malignant tumor of the urinary system, and resistance to the targeted drug sunitinib remains a major clinical challenge. This study investigated the mechanism underlying the action of Astragalus polysaccharide (APS) in RCC and demonstrated that APS can degrade ZEB1 via the ubiquitin proteasome pathway, downregulate the expression of downstream SCD1, and inhibit the Wnt/β-catenin signaling pathway. In vitro experiments revealed that the combination of APS and sunitinib significantly suppressed the proliferation, migration, and invasion of renal cancer cell lines such as 786-O and A498. Additionally, this combination promoted apoptosis and induced G1 phase cell cycle arrest. In vivo validation in a nude mouse xenograft model confirmed that this combined regimen synergistically reduced the tumor volume without causing obvious organ toxicity. Clinical data further verified that high ZEB1 expression is associated with poor prognosis in RCC and that ZEB1 promotes tumor progression by regulating SCD1 to activate the Wnt signaling pathway. In conclusion, APS enhances the sensitivity of RCC to sunitinib by targeting the ZEB1-SCD1-Wnt axis, thus providing a theoretical basis for the clinical application of this combined therapy.