Abstract
The platinum-based drug cisplatin is a widely used anticancer drug which acts by causing the induction of apoptosis. Some types of cancer have intrinsic or acquired resistance to cisplatin, however. A model of cisplatin resistance is provided by the cisplatin-resistant KB/CP4 human epidermoid cancer cell line. It was found previously in our laboratory that activity of the volume-sensitive, outwardly rectifying chloride channel (VSOR-ClC) is virtually absent in KB/CP4 cells. We hypothesized that the lack of VSOR-ClC current may contribute to cisplatin resistance in these cells. An attempt was made to restore the current in KB/CP4 cells so that the effect of its expression on cisplatin resistance could be tested. Treatment of KB/CP4 cells with trichostatin A (TSA), a histone deacetylase inhibitor, caused VSOR-ClC current to be partially restored. A cell viability assay showed that in response to cisplatin, viability of cells treated with TSA for 48 h decreased significantly compared to control cells. Moreover, a caspase-3 activity assay showed that TSA-treated cells underwent significantly increased apoptosis induced by cisplatin. These effects were blocked by simultaneous treatment of the cells with a VSOR-ClC blocker. From these results, we conclude that restoration of VSOR-ClC functional expression by TSA treatment leads to a decrease in cisplatin resistance and an increase in cisplatin-induced apoptosis in KB/CP4 cells. [J Physiol Sci. 2006;56 Suppl:S115]
