Purpose: Vitamin D compounds have been shown to inhibit tumor growth in a transgenic retinoblastoma murine model. The mechanism of action has not been defined clearly, although an antiangiogenic action has been proposed.
Methods: Transgenic retinoblastoma mice received high (0.05 microgram) and low (0.025 microgram) doses of vitamin D3 by intraperitoneal injection 5 times per week for 5 weeks. Control animals were injected with mineral oil vehicle alone. At 5 months of age, the animals were killed and eyes were enucleated and processed for light microscopy. Paraffin-embedded sections were stained with an immunoperoxidase stain (GS-1) specific for mammalian vascular endothelium. Sections were graded by a single masked reviewer, and intraobserver reliability was assessed. Mean vessel counts were made for each group.
Results: The high-dose group had the lowest mean vessel count (8.5), followed by the low-dose group (10.1). The control group had the highest mean vessel count (14.1). Vitamin D-treated animals (high- and low-dose groups combined) had significantly fewer vessels P = 0.001) than untreated controls.
Conclusions: These results support the hypothesis that inhibition of angiogenesis is a mechanism of action for vitamin D in the transgenic retinoblastoma mouse model.