Torii Koji, Yamada Suguru, Nakamura Kae, Tanaka Hiromasa, Kajiyama Hiroaki, Tanahashi Kuniaki, Iwata Naoki, Kanda Mitsuro, Kobayashi Daisuke, Tanaka Chie, Fujii Tsutomu, Nakayama Goro, Koike Masahiko, Sugimoto Hiroyuki, Nomoto Shuji, Natsume Atsushi, Fujiwara Michitaka, Mizuno Masaaki, Hori Masaru, Saya Hideyuki, Kodera Yasuhiro
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Gastric Cancer. 2015 Jul;18(3):635-43. doi: 10.1007/s10120-014-0395-6. Epub 2014 Jul 6.
Treatment of peritoneal carcinomatosis arising from gastric cancer remains a considerable challenge. In recent years, the anticancer effect of nonequilibrium atmospheric pressure plasma (NEAPP) has been reported in several cancer cell lines. Use of NEAPP may develop into a new class of anticancer therapy that augments surgery, chemotherapy, and radiotherapy.
Gastric cancer cells were assessed for changes in cell morphology and rate of proliferation after treatment with NEAPP-exposed medium (PAM). To explore the functional mechanism, caspase 3/7, annexin V, and uptake of reactive oxygen species (ROS) were evaluated, along with the effect of the ROS scavenger N-acetylcysteine (NAC).
PAM treatment for 24 h affected cell morphology, suggestive of induction of apoptosis. PAM cytotoxicity was influenced by the time of exposure to PAM, the type of cell line, and the number of cells seeded. Cells treated with PAM for 2 h demonstrated activated caspase 3/7 and an increased proportion of annexin V-positive cells compared with untreated cells. Additionally, ROS uptake was observed in PAM-treated cells, whereas NAC reduced the cytotoxicity induced by PAM presumably through reduction of ROS uptake. Furthermore, CD44 variant 9, which reportedly leads to glutathione synthesis and suppresses stress signaling of ROS, was overexpressed in PAM-resistant cells.
PAM treatment induced apoptosis of gastric cancer cells through generation and uptake of ROS. Local administration of PAM could develop into an option to treat peritoneal carcinomatosis.
胃癌引起的腹膜癌的治疗仍然是一项重大挑战。近年来,非平衡大气压等离子体(NEAPP)在几种癌细胞系中的抗癌作用已有报道。使用NEAPP可能会发展成为一种新型的抗癌疗法,可增强手术、化疗和放疗的效果。
评估胃癌细胞在用NEAPP处理过的培养基(PAM)处理后细胞形态和增殖速率的变化。为了探究其功能机制,评估了半胱天冬酶3/7、膜联蛋白V以及活性氧(ROS)的摄取情况,以及ROS清除剂N-乙酰半胱氨酸(NAC)的作用。
PAM处理24小时影响细胞形态,提示诱导凋亡。PAM的细胞毒性受暴露于PAM的时间、细胞系类型和接种细胞数量的影响。与未处理的细胞相比,用PAM处理2小时的细胞显示半胱天冬酶3/7激活,膜联蛋白V阳性细胞比例增加。此外,在PAM处理的细胞中观察到ROS摄取,而NAC可能通过减少ROS摄取降低了PAM诱导的细胞毒性。此外,据报道可导致谷胱甘肽合成并抑制ROS应激信号的CD44变体9在PAM耐药细胞中过表达。
PAM处理通过ROS的产生和摄取诱导胃癌细胞凋亡。局部给予PAM可能会发展成为治疗腹膜癌的一种选择。