Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA.
Anticancer Res. 2012 Mar;32(3):739-46.
To define the potential utility of 20-hydroxyvitamin D(3) (20(OH)D(3)) as a tumorostatic agent, we assessed its in vitro antiproliferative activity and its in vivo toxicity.
The antitumor activity of 20(OH)D(3) was tested against breast and liver cancer cell lines using colony formation assays. To assess in vivo toxicity, mice were injected with 5-30 μg/kg 20(OH)D(3) intraperitoneally each day for 3 weeks. Blood and organ samples were collected for clinical pathology analyses.
20(OH)D(3) displays similar tumorostatic activity towards MDA-MB-453 and MCF7 breast carcinomas, and HepG2 hepatocarcinoma, in a dose-dependent manner. This compound is not hypercalcemic, does not cause detectable toxicities in liver, kidney, or blood chemistry in mice at a dose as high as 30 μg/kg. In contrast, both 25(OH)D(3) and 1,25(OH)(2)D(3) caused severe hypercalcemia at a dose of 2 μg/kg.
20(OH)D(3) possesses high efficacy for inhibiting cancer cell proliferation in vitro and is non-toxic in vivo, supporting its further development as a potential anticancer therapeutic agent.
为了确定 20-羟维生素 D(3)（20(OH)D(3)）作为肿瘤抑制剂的潜在用途，我们评估了其体外抗增殖活性及其体内毒性。
使用集落形成测定法评估 20(OH)D(3)对乳腺癌和肝癌细胞系的抗肿瘤活性。为了评估体内毒性，每天将 5-30μg/kg 的 20(OH)D(3)腹腔内注射到小鼠中，持续 3 周。收集血液和器官样本进行临床病理分析。
20(OH)D(3)以剂量依赖性方式对 MDA-MB-453 和 MCF7 乳腺癌以及 HepG2 肝癌显示出相似的肿瘤抑制活性。在高达 30μg/kg 的剂量下，该化合物不会引起高钙血症，也不会在小鼠的肝脏、肾脏或血液化学中引起可检测的毒性。相比之下，25(OH)D(3)和 1,25(OH)(2)D(3)在 2μg/kg 的剂量下都会引起严重的高钙血症。
20(OH)D(3)在体外具有抑制癌细胞增殖的高效性，且在体内无毒性，支持其进一步开发为潜在的抗癌治疗剂。
