Reversible Increase in Resistance of A-431 Carcinoma Cells to TRAIL-Induced Apoptosis in Confluent Cultures Corresponds to a Decrease in Expression of DR4 and DR5 Receptors

— TRAIL (TNF alpha Related Apoptosis Inducing Ligand) cytokine is of great interest for the development of targeted antitumor drugs. We have previously found a reversible increase in tumour cell resistance to TRAIL-induced apoptosis in confluent cultures. In this work we show that increase in resistance of A-431 cells to TRAIL-induced death in confluent culture is associated with reduced expression of pro-apoptotic receptors DR4 and DR5 with absence of anti-apoptotic receptors DcR1 and DcR2 on cell surface. Decreased representation of DR4 and DR5 receptors on the cell surface is accompanied by a lack of activation of the pro-apoptotic protein Bid, effector caspase 3 under the action of recombinant protein izTRAIL, which leads to an increase in TRAIL resistance. Our results indicate that reversible increase in resistance of human carcinoma A-431 cells to TRAIL-induced apoptosis in confluent cultures is caused by decrease in expression of DR4 and DR5 receptors on cell surface.