Blockade of potassium ion transports enhances hypotonicity-induced cytocidal effects in gastric cancer

// Toshiyuki Kosuga 1 , Atsushi Shiozaki 1 , Michihiro Kudou 1 , Yuzo Yamazato 1 , Daisuke Ichikawa 1 , Shuhei Komatsu 1 , Hirotaka Konishi 1 , Kazuma Okamoto 1 , Katsutoshi Shoda 1 , Tomohiro Arita 1 , Ryo Morimura 1 , Yasutoshi Murayama 1 , Yoshiaki Kuriu 1 , Hisashi Ikoma 1 , Masayoshi Nakanishi 1 , Hitoshi Fujiwara 1 , Yoshinori Marunaka 2, 3 and Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan 2 Department of Molecular Cell Physiology and Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan 3 Japan Institute for Food Education and Health, St. Agnes’ University, Kyoto, Japan Correspondence to: Atsushi Shiozaki, email: shiozaki@koto.kpu-m.ac.jp Keywords: gastric cancer; peritoneal lavage; peritoneal dissemination; potassium channel; regulatory volume decrease Received: January 17, 2017      Accepted: August 07, 2017      Published: September 08, 2017 ABSTRACT Background: Peritoneal lavage with distilled water has been used for surgeries of various cancers to reduce peritoneal recurrence. This study examined whether blockade of potassium ion transports enhances hypotonicity-induced cytocidal effects in gastric cancer (GC). Results: A potassium channel blocker inhibited the occurrence of regulatory volume decrease (RVD) induced by mild hypotonic stimulation, and significantly enhanced cytocidal effects on GC cells. Incubating MKN45 cells with hypotonic solutions containing a potassium channel blocker significantly reduced the formation of peritoneal metastases in nude mice. Methods: The three human GC cell lines (HGC-27, Kato III, and MKN45) were exposed to mild hypotonic solutions, and the effects of blockade of potassium ion transports during hypotonic stimulation on cell volume changes and cell viabilities were examined. In the in vivo study, MKN45 cells stimulated with mild hypotonic solutions were intraperitoneally injected into nude mice, and the effects of blockade of potassium ion transports during hypotonic stimulation on the formation of peritoneal metastases were evaluated. Conclusions: Blockade of potassium ion transports enhances hypotonicity-induced cytocidal effects on GC cells, which may contribute to development of a novel lavage method for further reduction of peritoneal recurrence in GC.