A Comparison of the Effectiveness of 1–Hydroxyvitamin D2 in Human Retinoblastoma and Neuroblastoma Xenograft Models

Abstract

Abstract: : Purpose: Retinoblastoma and neuroblastoma are pediatric tumors that have many similarities including their standard treatment options. Neuroblastoma is the most common cancer in infancy with a poor prognosis in advanced cases. Vitamin D and its analogs have been shown to have antineoplastic activity in retinoblastoma, breast cancer, prostate cancer, and other tumors. Using retinoblastoma and neuroblastoma xenograft models, we investigated the effect of 1α–hydroxyvitamin D₂, a vitamin D analog, in both tumors and compared its efficacy in several in vivo models. Methods: Two murine models were used: Y79 xenograft human retinoblastoma model and SK–N–AS xenograft human neuroblastoma model. These mice were administered various doses of 1α–hydroxyvitamin D₂, a vitamin D analog with reduced calcium activity, via oral gavage. After 5 weeks, the mice were euthanized. The tumors were then measured; the sera evaluated for hypercalcemia; and the kidneys examined for calcifications. Results: In the mice receiving 0.3 µg of 1α–hydroxyvitamin D₂, the tumor sizes when compared to control tumors were noted to be 37.8% in Y79 xenograft human retinoblastoma model and 42.2% in SK–N–AS xenograft human neuroblastoma model. Serum calcium levels and mortality were comparable in both retinoblastoma and neuroblastoma models. Conclusions: 1α–hydroxyvitamin D₂ is effective in both retinoblastoma and neuroblastoma models. New compounds are currently being tested clinically in neuroblastoma. Information on vitamin D’s effectiveness in neuroblastoma would also be useful in regard to retinoblastoma.

Keywords: tumors • oncology • retinoblastoma