Doxorubicin resistant neuroblastoma cells secrete factors that activate AKT and attenuate cytotoxicity in drug-sensitive cells.

The present study aims to verify the hypothesis that tumor cells with acquired resistance to chemotherapy may secrete survival factors and thus, participate in the protection of drug-sensitive cells against drug toxicity. A human neuroblastoma cell line, SK-N-SH, and its doxorubicin resistant derivative, RDOX6, have been used. Conditioned medium from RDOX6 cells attenuated the cytotoxic response of SK-N-SH cells to doxorubicin. This protective effect was associated with activation of the Akt survival pathway and inhibition of caspase-3. These data indicate that secretion, by drug-resistant cells, of factors that activate anti-apoptotic pathways in drug-sensitive cells, may constitute a novel mechanism of drug resistance.