Leptin contributes to the protection of human leukemic cells from cisplatinum cytoxicity

Leptin (ob gene) and its cognate receptor (obr) are relevant for fat metabo lism. Obr shares homology with the IL-6 signal transducer gp130 and is expr essed in hematopoietic cells. Since cytokines and growth factors regulate b oth hematopoiesis and response to chemotherapy, we tested the hypothesis of whether leptin protects leukemic cells from cytotoxicity of cisplatinum. A ntisense phosphorothioate oligodeoxynucleotides (ODNs) and antisense peptid e nucleic acids (PNAs) complementary to the obr gene were first tested for their growth inhibitory activity in obr expressing leukemic cells. Liposome -mediated transfection of ODNs (1-2 mu M) or PNAs (0.01-1 mu M) inhibited g rowth up to 50%. Combination treatments of cisplatinum and 0.01 mu M PNA re duced growth more than cisplatinum alone. Vice versa, recombinant human lep tin (rhL) diminished cisplatinum-induced growth inhibition. Finally, we inv estigated whether rhL affects cisplatinum-induced DNA damage and repair in the housekeeping gene beta-actin by means of real time TaqMan(R) polymerase chain reaction. RhL reduced DNA damage and increased DNA repair. The effec ts are, however, modest and leptin is probably not the only player in the a rmory of growth factors which affect drug resistance.