Activation of the PI3K/Akt and MAPK signaling pathways antagonizes adriamycin-induced HL-60 leukemia cell apoptosis.

Adriamycin (ADM) is a drug used in the treatment of various types of cancer and exerts an antineoplastic effect mainly through the induction of apoptosis. Phosphoinositide 3 kinase (PI3K)/Akt and MAPK are fundamental survival pathways activated by exposure to most chemotherapeutical agents. However, the role of these pathways in the ADM-induced apoptosis of leukemia cells remains unclear. In the present study, ADM triggered dose-dependent cytotoxicity and resulted in a significant loss of cell viability in HL-60 cells. Moreover, treatment with ADM significantly reduced mitochondrial membrane potential (ΔΨm) in the cells. Akt and ERK activation was also detected, and the inhibition of these two pathways resulted in the enhancement of ADM-induced apoptosis. These results indicate that the PI3K/Akt and ERK survival pathways antagonize the chemotherapeutic effect of ADM. Thus, inhibiting these pathways may serve to enhance the effect of ADM.