Retinoids modulate cell proliferation, differentiation and apoptosis in a variety of tumour cells including leukaemia and
neuroblastoma, a childhood tumour of the sympathetic nervous system. 13-cis
retinoic acid is in clinical use against
minimal residual disease in
neuroblastoma, where the effect seems to depend on dose, scheduling and tumour mass. Novel
retinoids are searched for, to improve potency and lower toxicity. We investigated the effect of the synthetic
retinoid Ro 13-6307 on
neuroblastoma growth in vitro on SK-N-BE(2) and SH-SY5Y cells. Furthermore, effects on tumour growth and the toxicity profile were investigated in a rat xenograft model. Effects of
Ro 13-6307 were compared to 13-cis RA (
retinoic acid) in vitro and in vivo.
Neuroblastoma cells treated with 1 microM
Ro 13-6307 exhibited neuronal differentiation, decreased proliferation and accumulation of cells in G1 phase in at least the same magnitude as 5 microM 13-cis RA. No apoptosis was detected in vitro. Treatment of nude rats with
neuroblastoma using
Ro 13-6307, 0.12 mg p.o. daily, decreased
neuroblastoma growth in vivo, in terms of tumour volume during treatment and tumour weight at sacrifice (p < 0.05). In contrast,
Ro 13-6307, 0.08 mg p.o. daily, resulted in no significant reduction in tumour growth. All rats treated with
Ro 13-6307 gained less weight than control rats, but they exhibited no other signs of toxicity. The toxicity profile of
Ro 13-6307 was similar to what we found with 13-cis RA. Our preclinical results suggest that
Ro 13-6307 may be a candidate
retinoid for clinical oral
therapy of
neuroblastoma in children.