title: Enhancement of the cytocidal effects of hypotonic solution using a chloride channel blocker in pancreatic cancer cells.
abstract: BACKGROUND
  Tumor cells exfoliated during surgery for pancreatic cancer can cause peritoneal recurrence. Peritoneal lavage with distilled water has been performed during surgery, but there have been no systematic studies for its efficacy and no experimental data demonstrating the cytocidal effects of distilled water on pancreatic cancer cells. This study investigated the cytocidal effects of hypotonic shock and enhancement using chloride channel blocker in pancreatic cancer cells.
  
  
  METHODS
  Three human pancreatic cancer cell lines, KP4-1, PK-1, and PK45-H, were exposed to distilled water, and the resultant morphological changes were observed under a differential interference contrast microscope connected to a high-speed video camera. Analysis of cell volume changes was performed using a high-resolution flow cytometer. To investigate the cytocidal effects of water, re-incubation of cells was performed after exposure to hypotonic solution. Additionally, the effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), a Cl(-) channel blocker, on cells during exposure to hypotonic solution were analyzed.
  
  
  RESULTS
  Video recordings demonstrated that hypotonic shock induced cell swelling followed by cell rupture. Measurement of cell volume changes indicated that severe hypotonicity increased broken fragments of cancer cells within 5 min. Re-incubation experiments demonstrated the cytocidal effects of hypotonic shock. In all cell lines, treatment with NPPB increased cell volume by inhibiting regulatory volume decreases, which are observed during hypotonic shock, and enhanced the cytocidal effects of hypotonic solution.
  
  
  CONCLUSIONS
  These findings support the efficacy of peritoneal lavage with distilled water for pancreatic cancer and suggest that 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, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Nako
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.forename: Shuhei
authors.initials: S
authors.lastname: Komatsu
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Konishi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iitaka
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ishii
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ikoma
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kubota
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.forename: Toshiya
authors.initials: T
authors.lastname: Ochiai
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: D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D003603:Cytotoxins / Q000494:pharmacology*; D057168:Distillation; D005434:Flow Cytometry; D006801:Humans; D007038:Hypotonic Solutions / Q000494:pharmacology*; D009579:Nitrobenzoates / Q000494:pharmacology*; D009994:Osmolar Concentration; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000601:surgery*; D010533:Peritoneal Lavage / Q000379:methods*; D014867:Water / Q000494:pharmacology
chemical_list: D018118:Chloride Channels; D003603:Cytotoxins; D007038:Hypotonic Solutions; D009579:Nitrobenzoates; D014867:Water; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid