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

Toshiyuki Kosuga,Yoshinori Marunaka,Yuzo Yamazato,Hitoshi Fujiwara,Tomohiro Arita,Hisashi Ikoma,Yoshiaki Kuriu,Katsutoshi Shoda,Atsushi Shiozaki,Michihiro Kudou,Masayoshi Nakanishi,Eigo Otsuji,Daisuke Ichikawa,Ryo Morimura,Shuhei Komatsu,Hirotaka Konishi,Yasutoshi Murayama,Kazuma Okamoto

doi:10.18632/oncotarget.20736

Toshiyuki Kosuga, Yoshinori Marunaka + Show 16 more

Open Access

https://doi.org/10.18632/oncotarget.20736

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Abstract

BackgroundPeritoneal 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).ResultsA 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.MethodsThe 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.ConclusionsBlockade 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.

Highlights

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related death worldwide [1]
Blockade of potassium ion transports enhances hypotonicityinduced cytocidal effects on gastric cancer (GC) cells, which may contribute to development of a novel lavage method for further reduction of peritoneal recurrence in GC
We have reported that peritoneal lavage with distilled water (DW) is a useful prophylactic treatment for peritoneal recurrence because severe hypotonic stimulation induces cell swelling followed by rupture of cancer cells [10, 11]

Summary

Introduction

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related death worldwide [1]. We have reported that peritoneal lavage with distilled water (DW) is a useful prophylactic treatment for peritoneal recurrence because severe hypotonic stimulation induces cell swelling followed by rupture of cancer cells [10, 11]. Cancer cells, as well as non-cancerous cells, have the inherent potential to avoid their ruptures even under hypotonic stimulation via the mechanism of regulatory volume decrease (RVD) which involves potassium and chloride ion transports [11,12,13,14,15,16,17]. 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)

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