Rubidium ions as a novel therapeutic approach for glioblastoma

Glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options, mainly due to challenges such as incomplete resection and blood-brain barrier limitations. Rubidium, a naturally occurring alkali metal with favorable biocompatibility, widely used in myocardial and tumor perfusion imaging as a blood flow tracer, is repurposed in this study to investigate its potential therapeutic effects and mechanisms against GBM. The impacts of rubidium ions (Rb⁺) on GBM cells were assessed through functional assays evaluating proliferation, migration, invasion, and apoptosis. RNA sequencing and Western blot analyses were employed to investigate molecular mechanisms, while in vivo models were used to evaluate therapeutic efficacy and safety. Rb⁺ treatment significantly suppressed GBM cell proliferation, migration, and invasion, while inducing apoptosis and cell cycle arrest at the G2/M phase. Mechanistic studies revealed that Rb⁺ downregulated the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, contributing to the induction of apoptosis in tumor cells. In vivo, Rb⁺ exhibited potent anti-tumor activity with no detectable adverse effects on major organs, physiological functions, or behavior in mice. Our findings highlight Rb⁺ as a promising and innovative candidate for GBM therapy, leveraging the PI3K/AKT/mTOR pathway to inhibit tumor growth and promote apoptosis. This study underscores the potential of Rb⁺ in addressing the urgent need for novel GBM treatments, warranting further preclinical and clinical investigations.