Wang Y R, Wigington D P, Strugnell S A, Knutson J C
Bone Care International, 1600Aspen Commons, Middleton, WI 53562, USA.
Anticancer Res. 2005 Nov-Dec;25(6B):4333-9.
Active vitamin D compounds have been developed that maintain antiproliferative properties with low calcemic activity. BCI-210, a novel vitamin D pro-drug developed in our laboratory, is activated through side chain hydroxylation and possesses lower calcemic activity than calcitriol. The human hepatoma cell line (HepG2) was used to produce an active metabolite, which was characterized and identified as 27-hydroxy-BCI-210. We compared the ability of 27-OH-BCI-210 with calcitriol to inhibit proliferation of prostate (LNCaP), and breast (MCF-7) cancer cells. Cells were plated in multi-well plates and incubated with vehicle or vitamin D compounds for 6 days, after which the cell numbers were determined by a colorimetric assay. 27-OH-BCI-210 produced a dose-dependent growth inhibition, although a concentration five-fold greater than calcitriol was required to produce equivalent inhibition. We also examined the antiproliferative activity of 27-OH-BCI-210 in combination with chemotherapeutic drugs. With genistein and doxorubicin, 27-OH-BCI-210 produced synergistic inhibition of proliferation of LNCaP and MCF-7 cells. These synergistic interactions suggest the potential clinical utility of 27-OH-BCI-210 in the treatment of prostate and breast tumors.
已开发出具有低血钙活性且能维持抗增殖特性的活性维生素D化合物。BCI - 210是我们实验室研发的一种新型维生素D前药，通过侧链羟基化被激活，并且与骨化三醇相比具有更低的血钙活性。用人肝癌细胞系（HepG2）产生一种活性代谢物，经表征和鉴定为27 - 羟基 - BCI - 210。我们比较了27 - 羟基 - BCI - 210与骨化三醇抑制前列腺癌（LNCaP）和乳腺癌（MCF - 7）细胞增殖的能力。将细胞接种于多孔板中，用赋形剂或维生素D化合物孵育6天，之后通过比色法测定细胞数量。27 - 羟基 - BCI - 210产生了剂量依赖性的生长抑制作用，尽管需要比骨化三醇高五倍的浓度才能产生同等程度的抑制。我们还研究了27 - 羟基 - BCI - 210与化疗药物联合使用时的抗增殖活性。与染料木黄酮和阿霉素联合使用时，27 - 羟基 - BCI - 210对LNCaP和MCF - 7细胞的增殖产生协同抑制作用。这些协同相互作用表明27 - 羟基 - BCI - 210在治疗前列腺癌和乳腺癌方面具有潜在的临床应用价值。
