Therapeutic potential of asparagus polysaccharide in bladder cancer treatment via modulation of PI3K/AKT/mTOR signaling

Background Bladder cancer (BCa) is one of the most prevalent malignant tumors worldwide, with high incidence and recurrence rates, underscoring the urgent need for safe and effective therapeutic strategies. Recently, asparagus polysaccharide (ASP) has attracted attention for its diverse bioactivities, including anticancer, anti-inflammatory, and low-toxicity properties. However, its effects on BCa remain poorly understood. Objective This study aims to investigate the effects of ASP on bladder cancer cells and to elucidate the underlying molecular mechanisms. Methods The effects of ASP on T24 and 5637 bladder cancer cells were assessed using the cell counting Kit-8 (CCK-8), colony formation, wound healing, transwell invasion, TUNEL, and ROS assays. Western blot analysis was performed to assess apoptosis-related proteins (Bax, cleaved Caspase-3, Bcl-2) and key proteins of the PI3K/AKT/mTOR pathway. Additionally, IGF-1, a pathway activator, was used to explore ASP's mechanistic effects. Results ASP inhibited cell proliferation, migration, and invasion in a dose-dependent manner, and also induced apoptosis and elevated ROS levels. Western blot analysis revealed ASP-mediated downregulation of PI3K/AKT/mTOR signaling, as evidenced by reduced phosphorylation of PI3K, AKT, and mTOR. Co-treatment with IGF-1 partially reversed these effects, restoring phosphorylation of PI3K/AKT/mTOR components and cellular migration and invasion, indicating ASP's anticancer activity was mediated through this pathway. Conclusion ASP exerted anticancer effects in BCa by inhibiting PI3K/AKT/mTOR pathway, suppressing proliferation and invasion, and inducing apoptosis. These findings underscore ASP's potential as a novel therapeutic agent for bladder cancer treatment.