Resistance training and nanocurcumin modulate the p53 pathway in glioblastoma: Implications for inter-organ cross-talk

Glioblastoma multiforme (GBM) exhibits dysregulated p53 tumor-suppressor signaling, driving therapeutic resistance; exercise and nutraceuticals represent promising adjuvants for pathway modulation. This study investigated resistance training and nanocurcumin in an orthotopic GBM rat model (n=40), with groups including healthy controls, cancer controls, nanocurcumin (80 mg/kg/day), resistance training (ladder climbing, 50% BW + 30g, 3×/week), and combined intervention. After 4 weeks, tumor tissue analysis revealed resistance training significantly reduced p53 mRNA expression versus cancer controls (1.8 ± 0.2 vs. 3.1 ± 0.3; p = 0.021), while all interventions suppressed p21 (combination group: 1.2 ± 0.1 vs. control 4.0 ± 0.4; p < 0.001), demonstrating 70% greater p21 inhibition in the combined group versus monotherapies (p < 0.01). The synergistic p21 downregulation indicates potent disruption of the G1/S cell-cycle checkpoint, likely mediated through inter-organ cross-talk along the muscle-liver-brain axis—where exercise-induced myokines (IL-6, BDNF) mitigate tumor oxidative stress, nanocurcumin suppresses hepatic inflammatory mediators, and hemodynamic adaptations enhance blood-brain barrier penetration. These findings position resistance training and nanocurcumin as a novel non-pharmacological adjuvant strategy to potentiate conventional glioma therapies by leveraging systemic physiological communication.