Enhancement of the cytocidal effects of hypotonic solution using a chloride channel blocker in pancreatic cancer cells.

Yoshito Nako, Atsushi Shiozaki, Daisuke Ichikawa, Shuhei Komatsu, Hirotaka Konishi, Daisuke Iitaka, Hiromichi Ishii, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Toshiya Ochiai, Takashi Nakahari, Yoshinori Marunaka, Eigo Otsuji

Journal: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2013;12(5):440-8

PMID: 23127534

Full Text on Elsevier Science View on PubMed

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.

Address: Department of Surgery, Division of Digestive Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan.

DOI: 10.1016/j.pan.2012.08.003

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MeSH Terms: Cell Line, Tumor, Cell Size, Cell Survival, Chloride Channels, Cytotoxins, Distillation, Flow Cytometry, Humans, Hypotonic Solutions, Nitrobenzoates, Osmolar Concentration, Pancreatic Neoplasms, Peritoneal Lavage, Water