Ito Yuki, Kanda Mitsuro, Tanaka Hiromasa, Nakamura Kae, Mizuno Masaaki, Hori Masaru, Kajiyama Hiroaki, Kodera Yasuhiro
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Center for Low-temperature Plasma Sciences, Nagoya University, Nagoya, Japan.
Sci Rep. 2025 Jun 5;15(1):19807. doi: 10.1038/s41598-025-04977-3.
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.
用非平衡大气压等离子体辐照的液体具有抗肿瘤作用。在此，我们制备了质量浓度分别为1%、3%和5%的等离子体活化醋酸林格液（PAA）和等离子体活化醋酸钠（PASA）溶液。我们评估了PAA和PASA对胃癌（GC）的抗肿瘤作用。使用PAA、1% PASA、3% PASA和5% PASA对两种GC细胞系（MKN1-Luc和MKN45-Luc）以及正常人腹膜间皮细胞进行细胞活力测定。为阐明其功能机制，我们检测了3% PASA照射10分钟后诱导的形态学变化。为进一步阐明潜在的生物学过程，我们比较了未暴露于等离子体的3%醋酸钠溶液和照射10分钟的3% PASA给药后凋亡相关蛋白的表达。此外，将MKN45-Luc细胞腹腔注射到小鼠体内，随后腹腔注射未暴露于等离子体的醋酸林格液（对照1组）、未暴露于等离子体的3%醋酸钠溶液（对照2组）和照射10分钟的3% PASA（治疗组）。使用体内生物发光成像和剖腹术观察腹膜播散情况。PAA和PASA以醋酸钠浓度依赖性方式发挥抗肿瘤作用。与GC细胞相比，在等离子体暴露5分钟和10分钟时，PAA和3% PASA对正常腹膜间皮细胞的损伤明显更小（p < 0.001）。在GC细胞中，3% PASA处理1.5小时后观察到指示凋亡的泡状结构。3% PASA处理增加了磷酸化MKK3/MKK6和磷酸化p38 MAPK的表达，表明凋亡可能通过p38 MAPK途径介导。腹腔注射3% PASA显著减少了腹膜结节的数量，且未检测到不良事件。在此我们表明PASA对GC具有抗肿瘤作用，表明腹腔注射3% PASA可能成为GC腹膜播散的一种新的治疗方法。
