Red ginseng polysaccharide targets the PI3K/AKT/mTOR pathway to induce mitochondrial apoptosis in bladder cancer

Bladder cancer (BLC) is the tenth most prevalent malignancy worldwide, presenting substantial challenges to healthcare systems due to its high per-patient management costs. These costs are attributed to extended treatment durations, frequent follow-up care, and reliance on resource-intensive invasive procedures. Despite advancements in oncology, the development of effective therapies and improvements in patient quality of life for BLC have lagged behind those for other cancers, underscoring the need for innovative, less burdensome therapeutic strategies. To further explore the role of red ginseng polysaccharide (RGP) in BLC, this study assessed RGP's capacity to suppress tumor growth in an animal model and clarified the molecular mechanisms underlying BLC. The effects of RGP on BLC cells were investigated using real-time cell analysis and colony formation assays. To look into its mode of action, western blot analysis, immunofluorescence staining, and flow cytometric analysis were used. The results indicated that RGP significantly inhibits BLC cell proliferation and dose-dependently downregulates PI3K subunit expression. Additionally, RGP suppressed the activity of downstream signaling pathways, including AKT/mTOR and PKCα. It induced mitochondrial apoptosis in BLC cells by modulating the expression of BCL-2 family proteins, leading to mitochondrial dysfunction and programmed cell death. RGP exhibited significant anti-tumor and anti-proliferative effects, inducing mitochondrial apoptosis via the PI3K/BAD signaling pathway in an animal model and suppressing EGF-regulated protein expression in BLC. These findings highlight the preclinical potential of RGP, necessitating further clinical trials to assess its pharmacokinetics, safety, and therapeutic efficacy as a potential treatment for metastatic bladder cancer.