抄録
Modulation of ion permeability of the plasma membrane during the cell cycle is one of the key events in cell cycle progression. Our recent studies indicate that the intracellular chloride could act as a signal to regulate important cellular functions. The aim of the present study was to investigate whether the intracellular chloride affects cell growth and cell cycle progression of cancer cells. In human gastric cancer MKN28 cells, culture in the Cl−-replaced medium (replacement of NaCl by NaNO3) induced a significant decrease of the intracellular chloride concentration ([Cl−]i). A cell proliferation assay indicates that cell growth was significantly inhibited by the exposure of cells to the Cl−-replaced medium. We found that cells cultured in Cl−-replaced media showed cell cycle arrest at the G0/G1 phase, and that CDK2 and phosphorylated Rb were decreased in low Cl−-treated cells. Further analysis revealed that the exposure to Cl−-replaced media significantly increased expressions of p21 CDK inhibitor protein in a p53-independent manner. These findings suggest the regulation of [Cl−]i is a novel, unique therapeutic strategy for gastric cancer treatment. [J Physiol Sci. 2008;58 Suppl:S207]
