In vitro and in vivo preclinical chemotherapy studies of human neuroblastoma

Abstract

Two human neuroblastoma cell lines, LA-N-1 and SK-N-MC growing in vitro and as subcutaneous tumors in athymic nude mice, were evaluated for their sensitivity to cyclophosphamide, doxorubicin (Adriamycin), and vincristine. In vitro, cyclophosphamide, following liver S-9 metabolic activation, and vincristine were significantly more cytotoxic to SK-N-MC than to LA-N-1 cells; doxorubicin was equally cytotoxic to both cell types. Treatment of nude mice bearing LA-N-1 and SK-N-MC tumors with cyclophosphamide and vincristine produced significant reduction (> 50%) in SK-N-MC tumor weights but not in LA-N-1 tumor weights. Doxorubicin failed to produce significant reduction in the weight of either the LA-N-1 or the SK-N-MC tumor. These sensitivities were generally similar to the clinical response of the tumors to these same agents. Such an in vitro and in vivo system using these and other neuroblastoma cell lines may provide a preclinical model for evaluating the activity of chemotherapeutic agents against human neuroblastoma.