Administration of vitamin D3 improves antimetastatic efficacy of cancer vaccine therapy of Lewis lung carcinoma.

Abstract

AIM:

To analyze antitumor efficacy of experimental cancer vaccine therapy combined with introduction of vitamin D3 (VD3) for treatment of Lewis lung carcinoma (3LL).

MATERIALS AND METHODS:

Cancer vaccines composed from recombinant murine beta-defensin-2 (mBD-2) and 3LL cell lysate, or DNA, coding for mBD-2-Muc1 fusion construct cloned in pcDNA3+ vector, were prepared and used for intradermal vaccination. Experimental cancer vaccines introduced i. d. at therapeutic and prophylactic regimens to 3LL-bearing C57Bl mice, were applied alone or in combination with VD3 (administered per os) and/or low-dose cyclophosphamide (CP, administered intraperitoneal). Efficacy of treatments was analyzed by primary tumor growth dynamics indexes and by metastasis rate in vaccinated animals.

RESULTS:

As it has been shown, administration of the protein-based vaccine composed from mBD-2 and 3LL cell lysate in combination with VD3 and CP, but not in VD3 free setting, led to significant suppression of primary tumor growth (p < 0.005) and had significant antimetastatic effect. Introduction of VD3 with or without CP in the scheme of treatment with mBD- 2-Muc1-DNA vaccine at therapeutic regimen has led to significant suppression of primary tumor (p < 0.05) and metastasis volumes (p < 0.005), while in the groups of animals treated with DNA-vaccine + VD3 with or without CP at prophylactic regimen, significant antimetastatic effect (p < 0.05) and elevation of average life-span (p < 0.05) have been registered.

CONCLUSION:

The results of this pilot study have shown promising clinical effects of VD3 administration in combination with cancer vaccinotherapy in vivo.

• Authors: E Zhuravel, O Efanova, T Shestakova, N Glushko, O Mezhuev, M Soldatkina, P Pogrebnoy
• Journal: Experimental oncology (Exp Oncol) Vol. 32 Issue 1 Pg. 33-9 (Mar 2010) ISSN: 1812-9269 [Print] Ukraine
• PMID: 20332759 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Mucin-1
• beta-Defensins
• Cholecalciferol

Topics

• Animals
• Cancer Vaccines (therapeutic use)
• Carcinoma, Lewis Lung (genetics, pathology, therapy)
• Cells, Cultured
• Cholecalciferol (administration & dosage, pharmacology, therapeutic use)
• Combined Modality Therapy
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mucin-1 (genetics, metabolism)
• Neoplasm Metastasis
• Treatment Outcome
• beta-Defensins (genetics, metabolism)