This study aimed to assess, in an in vivo experimental model, the growth inhibitory effects of
IdB 1016 (
Silipide, a complex of
silybin/
phosphatidylcholine) when used as a single agent against human
ovarian cancer. We also wanted to investigate the mechanism of the antiangiogenic action by assessing
Vascular Endothelial Growth Factor (
VEGF) levels and by using macroarray technology to evaluate the regulation of a panel of genes involved in angiogenesis. We also aimed to establish the plasma and tumour bioavailability of
silybin after repeated administration of
IdB 1016. Female nude mice bearing human
ovarian cancer xenografts (A2780) received 450 mg/kg/day
IdB 1016 daily by oral gavage until the end of the study. At sacrifice, blood and tumour specimens were collected and subsequently processed for the determination of
silybin levels,
VEGF levels or a gene expression profile.
IdB 1016 was significantly active in inhibiting ovarian tumour growth. Treatment with 450 mg/kg/day for a total of 20 administrations produced a tumour weight inhibition (TWI%) of 78% and a Log10 Cell Kill (LCK) of 1.1. Free
silybin levels were found to be 7.0+/-5.3 microg/ml and 183.5+/-85.9 ng/g tissue (mean+/-standard deviation (S.D.)) in the plasma and tumour samples, respectively. No significant differences were found in the concentration of human
VEGF in xenografts from control and IdB 1016-treated mice. The array analysis suggested the downregulation of the VEGR receptor 3 and the upregulation of
angiopoietin-2 as potential mechanisms for the antiangiogenic activity. In conclusion, these findings suggest
IdB 1016 is a good candidate, with a relevant clinical potential, for use in the management of recurrent
ovarian cancer. A phase II, non-randomised clinical study is now ongoing in our Institute aimed at evaluating the efficacy of daily administrations of
IdB 1016 in the serological recurrence of
ovarian cancer.