Astragalus polysaccharides inhibits tumor proliferation and enhances cisplatin sensitivity in bladder cancer by regulating the PI3K/AKT/FoxO1 axis

Abstract

Cisplatin (DDP) resistance presents a major challenge in bladder cancer (BLCA) treatment. Recent evidence suggests that Astragalus polysaccharide (APS), extracted from Astragalus membranaceus, may sensitize tumors to DDP. However, the precise mechanisms by which APS modulates DDP sensitivity in BLCA are not fully elucidated. The study employed computational biology, bioinformatics, and both in vitro and in vivo experiments to explore the role of APS in BLCA. The results demonstrate that APS inhibits BLCA cell proliferation, induces apoptosis in vitro, and suppresses tumor growth in vivo. Additionally, APS induces G₀/G₁ cell cycle arrest in BLCA cells by downregulating CCND1 expression. Moreover, APS further enhances DDP-induced apoptosis by downregulating PI3K-p110β and p-AKT expression, while upregulating FoxO1 expression. Bioinformatics analysis indicates that APS may remodel the tumor microenvironment (TME) and influence cell-cell interactions, specifically through modulation of macrophage M2 polarization and CD8+ T cell exhaustion, thereby overcoming DDP resistance. In conclusion, APS potentiates DDP-induced apoptosis in BLCA cells via the PI3K/AKT/FoxO1 axis and may act as an immunomodulator to remodel the TME, offering a potential strategy to combat DDP resistance in BLCA.

Keywords: Astragalus polysaccharides; Bladder cancer; DDP resistance; PI3K/AKT/FoxO1 axis; Tumor microenvironment.