A 6-day in vitro growth-inhibition assay was used to determine relative sensitivity of six human
neuroblastoma cell lines to three classes of
cancer chemotherapeutic agents:
antimetabolites (
methotrexate,
methasquin, and
cytarabine);
antimitotics (
vincristine,
vinblastine,
vindesine,
colchicine, and
demecolcine); and
antibiotics (
dactinomycin and
doxorubicin). Human fibroblast lines served as a reference standard. Whereas response to
antimetabolites by four of five
neuroblastoma lines tested was similar to that of fibroblasts, SK-N-MC cells were significantly more sensitive (fivefold to 16-fold) to the three drugs. Human
neuroblastoma cell lines were also differentially sensitive to
antimitotics, especially to
vincristine. In particular, SK-N-MC, IMR-32, and LA-N-2 cells were threefold to 17-fold more sensitive to this
drug than were the SK-N-SH and SK-N-BE(2) lines. With the exception of SK-N-SH, all of the human
neuroblastoma lines were considerably more sensitive to
vincristine than were human fibroblasts. The same three highly
vincristine-responsive lines were also significantly more sensitive to the other alkaloidal drugs as compared to fibroblasts. However, human
neuroblastoma and fibroblastic cells responded similarly to the two
antibiotics. The only cellular attribute consistently correlated with greater sensitivity to the
antimitotics among the six cell lines tested was expression of the
neurotransmitter biosynthetic
enzyme choline acetyltransferase. A differential response to the
vinca alkaloids was also exhibited by clonal sublines of SK-N-SH. One subpopulation (SH-EP) expressing a nonneuronal, substrate-adherent, variant phenotype was at least fourfold to eightfold more
drug sensitive than its neuroblastic counterpart (SH-SY5Y) or the parental SK-N-SH population. In addition to confirming reports of clinical efficacy of the various classes of agents, these data have demonstrated a variation in response possibly related to type or degree of neuronal differentiation and emphasize the importance of understanding the phenotypic diversity commonly observed in
neuroblastoma.