Tumor Inhibition and Toxicity Studies of 1alpha-Hydroxyvitamin D2 and 1,25-Dihydroxy-16-ene-23-yne-Vitamin D3 in a Retinoblastoma Xenograft Model With Large Tumors

Abstract

Abstract: : Purpose: To test the ability of two vitamin D analogs, 1α-OH-D₂ and 16,23-D₃, to inhibit tumor growth in short-term treatment of athymic mice with large subcutaneous human retinoblastoma xenografts. Methods: 120 athymic mice were subcutaneously injected with 2 x 10⁶ human Y79 retinoblastoma cells. Tumors were allowed to reach approximately 2 cm³. Animals were randomized into one of four groups: 1α-OH-D₂ (0.2 µg/0.1 ml via oral gavage), 16,23-D₃ (0.35 µg/0.1 ml via intraperitoneal injection), gavage control (coconut oil, 0.1 ml), or intraperitoneal control (mineral oil, 0.1 ml). Treatment was given for 5X/week for five weeks. Tumor size and animal body weights were recorded 3X/week. Results: Mean change in tumor volume (volume at treatment end/volume at treatment start) over the treatment period for each vitamin D-treated group was significantly less than in the controls (1α-OH-D₂ vs. gavage control, p value = 0.0002; 16,23-D₃ vs. IP control, p value < 0.0001). The change in tumor volume was as follows: gavage control, 5.25 ; 1α-OH-D₂, 2.56; IP control, 5.22; and 16,23-D₃, 1.96. There was no statistical significant effect on tumor size between 1α-OH-D₂ and 16,23-D₃ (p = 0.3222). Conclusion: Vitamin D analogs can inhibit tumor size in large human retinoblastoma tumors without significant toxic side effects. These results are similar to previously reported findings in smaller Y79 xenograft tumors in athymic mice.

Keywords: retinoblastoma • pathobiology • oncology