Role of vitamin D(3) as a sensitizer to cryoablation in a murine prostate cancer model: preliminary in vivo study.
OBJECTIVE
Calcitriol has been reported to have antitumor efficacy in several cancers. In this study, we hypothesized that calcitriol may potentially function as a cryosensitizer that can enhance cryoablation, and we investigated several molecular marker changes in a murine model of prostate cancer.


METHODS
Murine prostate tumors (RM-9) were grown in male C57BL/6J mice subcutaneously with neoadjuvant intratumoral injection of calcitriol followed by cryoablation. The microenvironmental changes after cryoablation alone and in combination with calcitriol were analyzed in a comparative fashion using immunohistochemistry and Western blot analyses.


RESULTS
Both cryoablation and the combination group could suppress tumor growth after treatment compared with the control. At final pathologic assessment, a larger necrotic area was seen in the combination group (P = .026). Although microvessel density (CD31) and the area of hypoxia (pimonidazole) was not different between the control and combination groups, cell proliferation (Ki-67) significantly decreased in the combination treatment (P = .035). In Western blot analyses, several markers for apoptosis were expressed significantly higher with the combination treatment.


CONCLUSIONS
The synergistic effect of calcitriol with cryoablation was demonstrated because of enhanced antitumor efficacy by increasing necrosis and apoptosis and reduced cell proliferation. This study suggests that calcitriol is a potentially applicable reagent as a freeze sensitizer to cryoablation.
Kimura
Masaki
M
Duke Prostate Center and Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Rabbani
Zahid
Z
Mouraviev
Vladimir
V
Tsivian
Matvey
M
Caso
Jorge
J
Satoh
Takefumi
T
Baba
Shiro
S
Vujaskovic
Zeljko
Z
Baust
John M
JM
Baust
John G
JG
Polascik
Thomas J
TJ
D000818:Animals; D002762:Cholecalciferol / Q000494:pharmacology*; D003452:Cryosurgery / Q000379:methods*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011300:Preoperative Care; D011471:Prostatic Neoplasms / Q000601:surgery*; D014815:Vitamins / Q000494:pharmacology*
D014815:Vitamins; D002762:Cholecalciferol