Duke Prostate Center and Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Urology. 2010 Sep;76(3):764.e14-20. doi: 10.1016/j.urology.2010.03.041.
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.
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.
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.
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.
已有研究报道，骨化三醇在多种癌症中具有抗肿瘤作用。本研究中，我们假设骨化三醇可能具有作为冷冻增敏剂的潜力，能够增强冷冻消融的效果，并在前列腺癌的小鼠模型中研究了几种分子标志物的变化。
雄性 C57BL/6J 小鼠皮下种植 RM-9 前列腺肿瘤，瘤内注射骨化三醇作为新辅助治疗，然后进行冷冻消融。采用免疫组织化学和 Western blot 分析比较单独冷冻消融和联合骨化三醇治疗后微环境的变化。
与对照组相比，冷冻消融和联合治疗组均可抑制肿瘤生长。在最终的病理评估中，联合治疗组的坏死面积更大（P =.026）。尽管微血管密度（CD31）和缺氧区（pimonidazole）在对照组和联合组之间没有差异，但联合治疗组的细胞增殖（Ki-67）显著降低（P =.035）。Western blot 分析显示，联合治疗组表达的几种凋亡标志物明显更高。
骨化三醇与冷冻消融具有协同作用，通过增加坏死和凋亡，减少细胞增殖，从而增强抗肿瘤疗效。本研究表明，骨化三醇是一种潜在的可应用于冷冻消融的增敏剂试剂。
