Effects of 1,25-Dihydroxyvitamin D_3 [1,25(OH)_2D_3] and Its Analogues (EB1089 and Analog V) on Canine Adenocarcinoma (CAC-8) in Nude Mice

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The aim of this study is to determine the effects of 1,25(OH)_2D_3 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)_2D_3 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)_2D_3; 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<O.O5). 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)_2D_3, or EB1089. A reduction of tumor growth was observed in CAC-8-bearing mice treated with 1,25(OH)2_D_3 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 plasma ionized calcium comparable to nontumor-bearing mice. Tumor volumes of CAC-8-bearing mice treated with 1,25(OH)_2D_3 and its analogues were smaller than vehicle-treated CAC-8-bearing mice. This finding suggested an inhibitory effect on tumor cell growth.
公益社団法人日本薬学会の論文
2002-05-01

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