Responsiveness of human retinoblastoma and neuroblastoma models to a non-calcemic 19-nor Vitamin D analog.

Daniel Albert // Publications // Oct 01 2005

PubMed ID: 16055326

Author(s): Albert DM, Plum LA, Yang W, Marcet M, Lindstrom MJ, Clagett-Dame M, DeLuca HF. Responsiveness of human retinoblastoma and neuroblastoma models to a non-calcemic 19-nor Vitamin D analog. J Steroid Biochem Mol Biol. 2005 Oct;97(1-2):165-72. Epub 2005 Aug 1. PMID 16055326

Journal: The Journal Of Steroid Biochemistry And Molecular Biology, Volume 97, Issue 1 2, Oct 2005

OBJECTIVES To investigate the effectiveness of 2-methylene-19-nor-(20S)-1alpha-hydroxybishomopregnacalciferol (2MbisP) in inhibiting the growth of retinoblastoma (RB) and neuroblastoma (NB).

METHODS For the RB study, the xenograft athymic mouse/human retinoblastoma cell (Y-79) model and the transgenic beta-luteinizing hormone-large T antigen (LHbeta-Tag) mice were systemically treated with 2MbisP or vehicle for 5 weeks. For the NB study, the xenograft athymic mouse/human neuroblastoma cell (SK-N-AS) model was treated with 2MbisP or vehicle for 5 weeks. Tumor size and toxicity were assessed.

RESULTS In the xenograft models of RB and NB, 2MbisP caused statistically significant inhibition of tumor growth. Tumor growth inhibition was also observed in the transgenic RB mice, but did not achieve statistical significance. In all the groups, no biologically significant toxic effects were observed using the following variables: serum calcium levels, degree of kidney calcification, changes in body weight or survival.

CONCLUSIONS In athymic mice, 2MbisP was effective in inhibiting RB and NB growth compared with controls. A lesser effect was seen in the transgenic RB model. 2MbisP did not cause hypercalcemia or a significant increase in mortality.

CLINICAL RELEVANCE 2MbisP should be considered for use in clinical trials of RB and NB.