Role of vitamin D(3) as a sensitizer to cryoablation in a murine prostate cancer model: preliminary in vivo study.
Journal Article (Journal Article)
OBJECTIVES: 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.
Full Text
Duke Authors
Cited Authors
- Kimura, M; Rabbani, Z; Mouraviev, V; Tsivian, M; Caso, J; Satoh, T; Baba, S; Vujaskovic, Z; Baust, JM; Baust, JG; Polascik, TJ
Published Date
- September 2010
Published In
Volume / Issue
- 76 / 3
Start / End Page
- 764.e14 - 764.e20
PubMed ID
- 20599255
Electronic International Standard Serial Number (EISSN)
- 1527-9995
Digital Object Identifier (DOI)
- 10.1016/j.urology.2010.03.041
Language
- eng
Conference Location
- United States