Effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and its analogues (EB1089 and analog V) on canine adenocarcinoma (CAC-8) in nude mice

Biol Pharm Bull. 2002 May;25(5):642-7. doi: 10.1248/bpb.25.642.


The aim of this study is to determine the effects of 1,25(OH)2D3 and its analogues on tumor growth and body weight, changes in plasma ionized calcium, parathyroid hormone-related protein (PTHrP) production, bone resorption, and the distribution of the 1,25(OH)2D3 receptor (VDR) on tumors in nude mice-bearing the canine adenocarcinoma (CAC-8). Thirty-seven nude mice were implanted subcutaneously with CAC-8. Two weeks after implantation, the mice were divided into 5 groups and injected intraperitoneally 3 times/week for 4 weeks with 5 different substrates. Group I (nontumor-bearing mice) were injected with vehicle. Groups II through V were CAC-8-bearing mice injected with the following: Grp. II, vehicle; Grp. III, analog V; Grp. IV, 1,25(OH)2D3; and Grp. V, EB1089. Our results showed that mice body weight (% change) of CAC-8-bearing mice was significantly lower than those of nontumor-bearing mice (p<0.05). CAC-8-bearing mice treated with analog V maintained their body weight better than CAC-8-bearing mice treated with either vehicle, 1,25(OH)2D3, or EB1089. A reduction of tumor growth was observed in CAC-8-bearing mice treated with 1,25(OH)2D3 and its analogues; however, the reduction was not statistically significant compared to the vehicle-treated CAC-8-bearing mice. All CAC-8-bearing mice increased osteoclastic bone resorption and hypercalcemia. Immunohistochemical staining of CAC-8 with VDR antibody demonstrated a positive reaction in nuclei of tumor cells. In conclusion, CAC-8-bearing mice treated with analog V were more active and maintained their body weight better than other CAC-8-bearing groups. Analog V-treated mice also showed no toxic side effects of hypercalcemia despite an increase in plasmaionized calcium comparable to nontumor-bearing mice. Tumor volumes of CAC-8-bearing mice treated with 1,25(OH)2D3 and its analogues were smaller than vehicle-treated CAC-8-bearing mice. This finding suggested an inhibitory effect on tumor cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Body Weight / drug effects
  • Bone Resorption / drug therapy
  • Bone and Bones / anatomy & histology
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Calcitriol / analogs & derivatives*
  • Calcitriol / pharmacology*
  • Calcium / blood
  • Dogs
  • Immunoenzyme Techniques
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Parathyroid Hormone-Related Protein
  • Peptide Hormones / biosynthesis
  • Radioimmunoassay
  • Receptors, Calcitriol / metabolism


  • Antineoplastic Agents
  • Parathyroid Hormone-Related Protein
  • Peptide Hormones
  • Receptors, Calcitriol
  • Calcitriol
  • seocalcitol
  • Calcium