Abstract
Liquids irradiated with nonequilibrium atmospheric pressure plasma exert antitumor effects. Here, we produced plasma-activated acetated Ringer (PAA) and plasma-activated sodium acetate (PASA) solutions, each at 1%, 3%, and 5% mass concentrations. We evaluated the antitumor effects of PAA and PASA on gastric cancer (GC). Two GC cell lines (MKN1-Luc and MKN45-Luc) as well as normal human peritoneal mesothelial cells were subjected to cell viability assays using PAA, 1% PASA, 3% PASA, and 5% PASA. To elucidate the functional mechanisms, we examined morphological changes induced by 3% PASA following 10 min of irradiation. To further elucidate the underlying biological processes, we compared the expression of apoptosis-related proteins following the administration of 3% sodium acetate solution without plasma exposure and 3% PASA irradiated for 10 min. Additionally, MKN45-Luc cells were intraperitoneally injected into mice, followed by intraperitoneal administration of acetated Ringer's solution without plasma exposure (control-1 group), 3% sodium acetate solution without plasma exposure (control-2 group), and 3% PASA irradiated for 10 min (treatment group). Peritoneal dissemination was observed using in vivo bioluminescent imaging and laparotomy. PAA and PASA achieved an antitumor effect in a sodium acetate concentration-dependent manner. PAA and 3% PASA caused significantly less damage to normal peritoneal mesothelial cells compared to GC cells at 5 and 10 min of plasma exposure (p < 0.001). Blebs, indicative of apoptosis, were observed at 1.5 h after 3% PASA treatment in GC cells. 3% PASA treatment increased the expression of phosphorylated MKK3/MKK6 and phosphorylated p38 MAPK, suggesting that apoptosis may be mediated through the p38 MAPK pathway. The intraperitoneal administration of 3% PASA significantly reduced the number of peritoneal nodules, and no adverse events were detected. Here we show that PASA exerted an antitumor effect on GC, indicating that the intraperitoneal administration of 3% PASA may serve as a novel treatment for the peritoneal dissemination of GC.