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

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

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2012 Sep-Oct

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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. 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. 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. 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. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Citation

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. Enhancement of the cytocidal effects of hypotonic solution using a chloride channel blocker in pancreatic cancer cells. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2012 Sep-Oct;12(5):440-8