title: Blockade of chloride ion transport enhances the cytocidal effect of hypotonic solution in gastric cancer cells.
abstract: BACKGROUND
  Cancer cells that are exfoliated into the peritoneal cavity during surgery are viable and have the potential to produce peritoneal recurrence. Although peritoneal lavage with distilled water is applied in some cancer surgeries to kill tumor cells, there is no consensus regarding the optimal methodology and its effects.
  
  
  METHODS
  Three human gastric cancer cell lines, MKN28, MKN45, and Kato-III, were exposed to distilled water, and the resultant morphologic changes were observed using a microscope. Analysis of cell volume changes was performed using a flow cytometer. To investigate the cytocidal effects of the water, re-incubation of the cells was performed after exposing them to hypotonic solution. Additionally, the effects of 5-nitro-2-3-phenylpropylamino)-benzoic acid (NPPB), a Cl(-) channel blocker, and R(+)-[(dihydroindenyl)oxy] alkanoic acid (DIOA), a blocker of the K(+)/Cl(-) co-transporter, on the cells during their exposure to hypotonic solution were analyzed.
  
  
  RESULTS
  After the cells had been exposed to the distilled water, a rapid increase in cell volume occurred followed by cell rupture. In the MKN45 and Kato-III cells, treatment with NPPB increased cell volume by inhibiting regulatory volume decrease and enhanced the cytocidal effects of the hypotonic solution, whereas no such effects were observed in the MKN28 cells. On the other hand, treatment of the MKN28 cells with DIOA inhibited RVD and enhanced the cytocidal effects of hypotonic shock.
  
  
  CONCLUSIONS
  These findings support the efficacy of peritoneal lavage with distilled water during surgery for gastric cancer and suggest that the regulation of Cl(-) transport enhances the cytocidal effects of hypotonic shock.
authors.affiliation: Department of Surgery, Division of Digestive Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iitaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kosuga
authors.forename: Shuhei
authors.initials: S
authors.lastname: Komatsu
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ishii
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakahari
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Marunaka
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary* / Q000601:surgery; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D007038:Hypotonic Solutions / Q000633:toxicity*; D007432:Intraoperative Period; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009579:Nitrobenzoates / Q000633:toxicity*; D009994:Osmolar Concentration; D009997:Osmotic Pressure / Q000187:drug effects; D010529:Peritoneal Cavity / Q000473:pathology; D010533:Peritoneal Lavage / Q000379:methods; D013274:Stomach Neoplasms / Q000556:secondary* / Q000601:surgery; D014867:Water / Q000494:pharmacology
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D007038:Hypotonic Solutions; D009579:Nitrobenzoates; D014867:Water; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid