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Updated: Jul 14, 2026
Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line
Published on: February 17, 2016
1 alpha-Hydroxyvitamin D2 inhibits growth of human neuroblastoma
Paul R van Ginkel1, William Yang, Marcus M Marcet
1Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, K6/412 CSC, Madison, WI 53792, USA.
Abstract:
Neuroblastoma is the most common extracranial solid tumor in childhood. The poor outcomes of patients with high-risk neuroblastoma have encouraged the search for new therapies. In the current study, the effect of the vitamin D analog 1alpha-hydroxyvitamin D2 (1alpha-OH-D2, doxercalciferol) was assessed in a mouse xenograft model of human neuroblastoma. Vitamin D receptor (VDR) expression levels in seven neuroblastoma cell lines were compared using real-time PCR. SK-N-AS cells, which express relatively high levels of VDR, were injected into the flanks of 60 mice. The mice were treated daily via oral gavage for 5 weeks with vehicle (control), 0.15 microg, or 0.3 microg of 1alpha-OH-D2. The animals were then euthanized, and tumors, sera, and kidneys were collected and analyzed. End tumor volumes were significantly smaller in both the 0.15 microg group (712.07 mm3, P = 0.0121) and 0.3 microg group (772.97 mm3, P = 0.0209) when compared to controls (1,681.75 mm3). In terms of toxicity, serum calcium levels were increased but mortality was minimal in both treatment groups. These results were similar to those previously described in the transgenic (LHbeta-Tag) and human xenograft (Y-79) models of retinoblastoma, a related tumor. In vitro cell viability studies of SK-N-AS and NGP cells, which represent two major human neuroblastoma subtypes that differ in their genetic abnormalities as well as their VDR expression levels, show that both are sensitive to calcitriol, the active metabolite of vitamin D3. In conclusion, the present study shows that 1alpha-OH-D2 can inhibit human neuroblastoma growth in vivo with relatively low toxicity. The safety of 1alpha-OH-D2 has been extensively studied; the drug is FDA-approved for the treatment of adult kidney patients, and Phase I/II trials have been conducted in adult oncology patients. There should not be major obstacles to starting Phase I and II clinical trials with this drug in pediatric patients with high-risk neuroblastoma.
Insights
The vitamin D analog 1alpha-hydroxyvitamin D2 (1alpha-OH-D2) effectively inhibited human neuroblastoma tumor growth in a mouse model with minimal toxicity. This suggests potential for clinical trials in high-risk pediatric neuroblastoma patients.
Area of Science:
- Oncology
- Pharmacology
- Pediatric Medicine
Background:
- Neuroblastoma is the most common childhood extracranial solid tumor.
- High-risk neuroblastoma patients have poor outcomes, necessitating novel therapeutic strategies.
- Vitamin D and its analogs are being investigated for anti-cancer properties.
Purpose of the Study:
- To evaluate the efficacy and toxicity of 1alpha-hydroxyvitamin D2 (1alpha-OH-D2) in a human neuroblastoma xenograft mouse model.
- To assess the impact of 1alpha-OH-D2 on tumor growth and serum calcium levels.
Main Methods:
- Compared Vitamin D Receptor (VDR) expression in neuroblastoma cell lines.
- Injected human neuroblastoma SK-N-AS cells into mice and treated with vehicle or 1alpha-OH-D2 (0.15 or 0.3 microg).
- Analyzed tumor volumes, serum calcium, and kidney tissues post-treatment.
Main Results:
- 1alpha-OH-D2 significantly reduced end tumor volumes in both treatment groups compared to controls.
- Treatment with 1alpha-OH-D2 led to increased serum calcium levels but minimal mortality.
- In vitro studies showed neuroblastoma cell lines are sensitive to calcitriol, the active vitamin D3 metabolite.
Conclusions:
- 1alpha-OH-D2 demonstrates in vivo efficacy in inhibiting human neuroblastoma growth with a manageable toxicity profile.
- The established safety of 1alpha-OH-D2 in adults supports its potential for clinical trials in pediatric high-risk neuroblastoma.
- Further investigation into vitamin D analogs as a therapeutic approach for neuroblastoma is warranted.
