Recent studies show that ion channels/transporters play important roles in fundamental cellular functions that would be involved in the cancer process. We review the evidence for their expression and functioning in human gastric cancer (GC), and evaluate the potential of cellular physiological approach in clinical management. Various types of ion channels, such as voltage-gated K(+) channels, intracellular Cl(-) channels and transient receptor potential channels have been found to express in GC cells and tissues, and to control cell cycles. With regard to water channels, aquaporin 3 and 5 play an important role in the progression of GC. Regulators of intracellular pH, such as anion exchanger, sodium-hydrogen exchanger, vacuolar H(+)-ATPases and carbonic anhydrases are also involved in tumorigenesis of GC. Their pharmacological manipulation and gene silencing affect cellular behaviours, suggesting their potential as therapeutic targets for GC. Our studies indicate the intracellular Cl(-) concentration could act as a mediator of cellular signaling and control cell cycle progression in GC cells. Further, we demonstrate the cytocidal effects of hypotonic shock on GC cells, and indicate that the blockade of Cl(-) channels/transporters enhances these effects by inhibiting regulatory volume decrease. A deeper understanding of molecular mechanisms may lead to the discovery of these cellular physiological approaches as a novel therapeutic strategy for GC.
Keywords: Gastric cancer; Intracellular chloride; Intracellular pH; Ion channels; Osmolality; Water channels.