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

Exp Oncol. 2010 Mar;32(1):33-9.

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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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