Role of vitamin D(3) as a sensitizer to cryoablation in a murine prostate cancer model: preliminary in vivo study.

Published

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

Pubmed Central 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