OBJECTIVENeuroblastoma (NB) is one of the most common solid tumors of early childhood. A small percentage of NB has been found to undergo spontaneous or chemotherapeutically induced regression or differentiation into benign ganglioneuromas. The differentiation therapy is a respective method in the clinical treatment of NB.

OBJECTIVEInterferon-gamma (IFN-gamma), nerve growth factor (NGF), and combination of IFN-gamma and NGF were used as induction drugs respectively to induce the differentiation of human SMS-KCNR cells. The cells were observed for morphological differences, growth arrest, and the TrkA mRNA expression of the 10th day-cells.

METHODSThe human SMS-KCNR cell lines were cultured. The TrkA mRNA expression was detected by RT-PCR. Cell counts were measured by using a hemocytometer and the viability was assessed with the trypan blue exclusion. The morphological differentiation was observed under the phase-contrast microscope.

RESULTSThe simultaneous loading of NGF with IFN-gamma caused more prominent neurite outgrowth than independent treatment with either IFN-gamma or NGF in SMS-KCNR cells (P < 0.01). The cell proliferation was inhibited significantly in the former (P < 0.01). The TrkA mRNA level increased in the IFN-gamma group (P < 0.01). While there was no significant change of TrkA mRNA level in the NGF group (P > 0.05). The TrkA mRNA level was obvious decreased in the combination group (P < 0.01).

CONCLUSIONIn human SMS-KCNR cells, the combination of IFN-gamma and NGF showed prominent effect on the cell differentiation. In contrast with the induction of TrkA mRNA expression by IFN-gamma, the combination treatment could decrease TrkA mRNA expression, which might indicate that a kind of negative feedback mechanism existed. These data suggest that using IFN-gamma and NGF together may be an appropriate strategy in the treatment of children with advanced neuroblastoma.