| Popis: |
Although increasing data indicates inhibitory roles of calcitriol on tumor growth in humans, little is known about its effects on canine tumors. The objectives of this study are to investigate the effects of calcitriol and its analogs on canine transitional cell carcinoma and canine prostate tissue explants. First, we investigated effects of calcitriol, seocalcitol and medium-chain triglyceride (MCT) on a canine transitional cell carcinoma cell line (TCC). The effects of calcitriol and seocalcitol on cell growth, cell cycle, vitamin D receptor (VDR) and Bcl-2 expression were determined with/without MCT. Second, we established a canine TCC mouse-xenograft model and used this model to examine effects of calcitriol, seocalcitol, and piroxicam on tumor growth. Third, the effects of calcitriol and dihydrotestosterone (DHT) were evaluated on arginine esterase (AE) acitivity and VDR expression in normal canine prostate tissue explants. In summary, our results showed that the VDR is present in canine TCC tumor and in the canine prostate. Calcitriol and seocalcitol significantly inhibited cell growth and calcitriol caused cell cycle arrest. Bcl-2 expression was decreased in cells treated with these compounds, although no significant changes in VDR expression were observed. MCT enhanced the growth-inhibitory effects of both compounds. We developed and used a canine TCC-mouse xenograft model to evaluate and compare the inhibitory effects of calcitriol, seocalcitol and piroxicam. Results showed that only seocalcitol reduced tumor volume compared to controls. The inhibitory effect of seocalcitol on tumor growth was supported by data from a Ki-67 staining. Blood calcium was higher in both calcitriol-and seocalcitol-treated mice compared to controls. In summary, our findings suggest a potential use for calcitriol and seocalcitol for the treatment canine TCC. We demonstrated that DHT increased AE activity and VDR expression in canine prostate tissue explants; however, there was no increase in AE activity in calcitriol-treated explants and a decreased in VDR expression. These results indicated that canine prostate tissue explants are a valuable model for the study of prostate pathobiology and pharmaceutical interventions. They also provided a basis for further investigation of roles of calcitriol as a therapeutic/preventative agent in benign prostatic hyperplasia in both dogs and humans. |
