The Journal of Physiological Sciences

, Volume 67, Issue 3, pp 353–360 | Cite as

Regulation of osmolality for cancer treatment



Disseminated metastasis is associated with a poor prognosis, and its management in the peritoneal or pleural cavity is crucial in the treatment of cancer. Recent studies show that ion and water transporters play important roles in fundamental cellular functions, including the regulation of cell volume that would be involved in the cancer process. Here, we review the evidence for hypotonic treatments of cancer and evaluate the potential of the cellular physiological approach in clinical management. The regulation of extracellular osmolality is a promising method, with several studies demonstrating the cytocidal effects of hypotonic solution on cancer cells. Peritoneal lavage with distilled water (DW) during surgery is reported to improve the survival rate of patients with spontaneously ruptured hepatocellular carcinoma. The in vitro studies included in this review also indicate the cytocidal effects of hypotonic shock on esophageal, gastric, colonic, pancreatic, and liver cancer cells with several unique methods and apparatuses, such as a differential interference contrast microscope connected to a digital video camera, a high-resolution flow cytometer and re-incubation analysis. The in vivo studies demonstrate the safeness of a peritoneal injection of DW into mice and indicate that the development of dissemination nodules can be prevented by the pre-incubation of cancer cells with DW or the peritoneal injection of DW. We also demonstrate that the blockade of Cl channels/transporters enhances the cytocidal effects of hypotonic shock by inhibiting regulatory volume decrease in various cancer cells. A deeper understanding of molecular mechanisms may lead to the discovery of these cellular physiological approaches as a novel therapeutic strategy for disseminated metastasis.


Disseminated metastasis Cancer Hypotonic treatment Regulatory volume decrease Cl channel 



The authors would like to thank Dr. Michihiro Kudou for technical assistance with the experiments.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© The Physiological Society of Japan and Springer Japan 2017

Authors and Affiliations

  1. 1.Division of Digestive Surgery, Department of SurgeryKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Department of Molecular Cell Physiology, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  3. 3.Department of Bio-Ionomics, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  4. 4.Japan Institute for Food Education and HealthSt. Agnes’ UniversityKyotoJapan

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