Takeda Shigeomi, Yamada Suguru, Hattori Norifumi, Nakamura Kae, Tanaka Hiromasa, Kajiyama Hiroaki, Kanda Mitsuro, Kobayashi Daisuke, Tanaka Chie, Fujii Tsutomu, Fujiwara Michitaka, Mizuno Masaaki, Hori Masaru, Kodera Yasuhiro
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ann Surg Oncol. 2017 May;24(5):1188-1194. doi: 10.1245/s10434-016-5759-1. Epub 2017 Jan 5.
The administration of fluid irradiated with non-equilibrium atmospheric pressure plasma (NEAPP) has attracted much interest as a novel therapeutic method for cancer. The authors previously reported on the efficacy of plasma-activated medium (PAM) for treating cancer cell lines through the induction of apoptosis. In this study, the therapeutic effect of PAM was evaluated in vivo using a peritoneal metastasis mouse model.
Two gastric cancer cell lines were used in proliferation assays performed to optimize the production of PAM by changing the distance between the plasma source and the medium surface and by altering the volume of irradiated medium. Wound-healing and adhesion assays were conducted to determine the effect of PAM therapy on cell migration and adhesion capacity in vitro. Finally, a mouse model established by the intraperitoneal injection of enhanced green fluorescent protein-tagged gastric cancer cells was used to explore the efficacy of PAM administered intraperitoneally in inhibiting peritoneal metastasis formation.
Shorter distances between the plasma source and the medium surface and smaller volumes of treated medium increased the anti-tumor effect of PAM. The PAM treatment attenuated gastric cancer cell migration and adhesion in vitro. The intraperitoneal administration of PAM decreased the formation of peritoneal metastatic nodules by 60% in the mouse model, and no adverse events were observed.
Plasma-activated liquids may represent a novel therapeutic method for the treatment of peritoneal metastases in gastric cancer.
用非平衡大气压等离子体(NEAPP)照射液体作为一种新型癌症治疗方法已引起广泛关注。作者之前报道了等离子体激活介质(PAM)通过诱导凋亡治疗癌细胞系的疗效。在本研究中,使用腹膜转移小鼠模型在体内评估了PAM的治疗效果。
在增殖试验中使用两种胃癌细胞系,通过改变等离子体源与培养基表面之间的距离以及改变照射培养基的体积来优化PAM的产生。进行伤口愈合和黏附试验以确定PAM疗法对体外细胞迁移和黏附能力的影响。最后,使用通过腹腔注射增强型绿色荧光蛋白标记的胃癌细胞建立的小鼠模型来探索腹腔注射PAM抑制腹膜转移形成的疗效。
等离子体源与培养基表面之间的距离越短以及处理的培养基体积越小,PAM的抗肿瘤效果越好。PAM处理减弱了体外胃癌细胞的迁移和黏附。在小鼠模型中,腹腔注射PAM使腹膜转移结节的形成减少了60%,且未观察到不良事件。
等离子体激活液体可能是一种治疗胃癌腹膜转移的新型治疗方法。