Science Topics - 50

Involvement of Ion Channel in Anticancer Drug Resistance
Elbert L. Lee*

Resistance of cancer cells to drug treatment is a major problem in cancer therapy.  The platinum-based drug cisplatin is a widely used anticancer drug which acts mainly by forming adducts with DNA that cause the induction of apoptosis. However, some types of cancer have intrinsic or acquired resistance to cisplatin. The cisplatin-resistant KCP-4 cell line serves as a model of acquired cisplatin resistance. It is known that activation of the volume-sensitive outwardly rectifying (VSOR) chloride channel, a channel involved in cell volume regulation, plays an important role in the progression of apoptosis, so we investigated the level of VSOR chloride channel activity in KCP-4 cells. It was found that functional expression of the channel, observed in whole-cell patch-clamp recordings, was virtually absent. Hypothesizing that the absence of VSOR chloride channel activity contributed to cisplatin resistance, we attempted to restore activity of the channel in these cells. Treatment with a histone deacetylase inhibitor, trichostatin A, caused a partial restoration of VSOR chloride channel activity which led to a decrease in cisplatin resistance, as measured by cell viability and caspase-3 activity assays. From these results we conclude that impaired activity of the VSOR chloride channel is involved in the cisplatin resistance of KCP-4 cancer cells (J. Cell. Physiol. 211: 513-521, 2007).



Lee EL, Shimizu T, Ise T, Numata T, Kohno K, Okada Y. Impaired activity of volume-sensitive Cl´╝Źchannel is involved in cisplatin resistance of cancer cells.  J. Cell. Physiol. 211: 513-521, 2007

 


*Division of Correlative Physiology, Department of Cell Physiology, National Institute for Physiological Sciences