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.
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.
Kunakornsawat
Sunee
S
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus 43210-1092, USA.
Rosol
Thomas John
TJ
Capen
Charles Chabert
CC
Reddy
Gudimetla Satyanarayana
GS
Binderup
Lise
L
Inpanbutr
Nongnuch
N
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy; D001842:Bone and Bones / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D004285:Dogs; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones / Q000096:biosynthesis; D011863:Radioimmunoassay; D018167:Receptors, Calcitriol / Q000378:metabolism
D000970:Antineoplastic Agents; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones; D018167:Receptors, Calcitriol; D002117:Calcitriol; C078903:seocalcitol; D002118:Calcium