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

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Abstract

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
JournalUrology
Volume76
Issue number3
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Urology

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    Kimura, M., Rabbani, Z., Mouraviev, V., Tsivian, M., Caso, J., Satoh, T., Baba, S., Vujaskovic, Z., Baust, J. M., Baust, J. G., & Polascik, T. J. (2010). Role of vitamin D3 as a sensitizer to cryoablation in a murine prostate cancer model: Preliminary in vivo study. Urology, 76(3), 764.e14-764.e20. https://doi.org/10.1016/j.urology.2010.03.041