GAMMA-INTERFERON AND RETINOIC ACID SYNERGIZE IN INHIBITING THE GROWTH OF HUMAN NEUROBLASTOMA-CELLS IN NUDE-MICE

We have investigated the effects of retinoic acid (RA), human recombinant gamma interferon (gamma-IFN), and the association of both agents on the growth of human neuroblastoma (NB) cells in [CD1(nu/nu)] nude mice. Two human NB cell lines, namely LAN-5 and GI-LI-N, were previously adapted to grow in syngeneic animals for 7 consecutive passages. At the eight passage, only animals which developed 10-mm diameter tumors within 40 days from xenograft were admitted to the study. RA and/or gamma-IFN were administered subcutaneously 3-5 days per week for 3 consecutive weeks. The number of days necessary for each tumor mass to grow up to 20 mm diameter (in vivo doubling time, ivDT) was then evaluated. Tumor growth was significantly inhibited in gamma-IFN (P < 0.005) and RA (P < 0.05) treated mice grafted with GI-LI-N. The combination of the two agents did not further enhance ivDT. The tumor growth inhibition was not statistically significant in LAN-5 bearing mice treated with RA or gamma-IFN alone, while a synergistic effect between the two drugs was observed (P < 0.05). We conclude that parenteral combined administration of RA and gamma-IFN may prove to be useful in inhibiting the growth of tumors derived from human NB cells resistant to single inducers.