LY294002, an inhibitor of phosphatidylinositol-3-kinase, causes preferential induction of apoptosis in human multidrug resistant cells.

Protein kinase B (PKB), a kinase downstream of phosphatidylinositol 3-kinase (PI3-kinase) provides anti-apoptotic and survival signals via phosphorylation of various targets. Inhibiting PI3-kinase with a 12 h exposure to 10 microM LY294002 induces levels of apoptosis of 30.39+/-1.53% in the KB-V1 multidrug resistant (MDR) cell line compared to 4.54+/-1.00% in drug sensitive KB-3-1 cells (P<0.001). This occurred in conjunction with a preferential reduction in activated PKB in MDR cells. These results suggest the PI3-kinase/PKB signalling pathway is important for the survival of MDR cells and inhibition of this pathway results in the selective induction of apoptosis in MDR cells.