Role of vitamin D3 as a sensitizer to cryoablation in a murine prostate cancer model: Preliminary in vivo study

Masaki Kimura, Zahid Rabbani, Vladimir Mouraviev, Matvey Tsivian, Jorge Caso, Takefumi Satoh, Shiro Baba, Zeljko Vujaskovic, John M. Baust, John G. Baust, Thomas J. Polascik

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)764.e14-764.e20
Issue number3
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Urology


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