Plasma-Activated Saline Resensitizes Cisplatin-Resistant T24 Bladder Cancer Cells

Plasma-activated saline (PAS) loads reactive oxygen and nitrogen species, triggering oxidative stress and tumor death. However, PAS exhibits poor anticancer efficacy due to rapid dilution and reactive species decay. Herein, we developed a plasma bubble reactor to activate saline and investigate its synergy with cisplatin (DDP) against DDP-resistant T24 bladder cancer cells (T24/DDP) in vitro. The results showed that PAS-DDP significantly reduced the cell viability of T24/DDP to 32.4%, surpassing PAS (52.9%) or DDP alone (96.9%). PAS-DDP significantly inhibited T24/DDP cells by intracellular reactive oxygen species accumulation, mitochondrial depolarization, and cell apoptosis induction. Moreover, PAS-DDP suppressed the p62/Keap1/Nrf2 signaling pathway, restoring oxidative sensitivity and boosting DDP efficacy. These findings suggest that PAS could enhance chemotherapy efficacy and overcome drug resistance.