Department of Physiology-CIMUS, Endocrine Oncology Laboratories (P1L3), Avda. Barcelona s/n, Campus Vida-University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
Cancers (Basel). 2013 Dec 27;6(1):67-78. doi: 10.3390/cancers6010067.
It has been demonstrated that 1,25-dihydroxyvitamin D3 (1,25D) and some of its analogues have antitumor activity. 1,25D labeled with deuterium (26,26,26,27,27,27-hexadeuterated 1a,25-dihydroxyvitamin D3, or 1,25D-d6) is commonly used as internal standard for 1,25D liquid chromatography-mass spectrometry (LC-MS) quantification. In the present study using human breast cancer cell lines, the biological activity of 1,25D-d6 administered alone and in combination with two commonly used antineoplastic agents, 5-fluorouracil and etoposide, was evaluated. Using an MTT assay, flow cytometry, and western blots, our data demonstrated that 1,25D-d6 has effects similar to the natural hormone on cell proliferation, cell cycle, and apoptosis. Furthermore, the combination of 1,25D-d6 and etoposide enhances the antitumoral effects of both compounds. Interestingly, the antitumoral effect is higher in the more aggressive MDA-MB-231 breast cancer cell line. Our data indicate that 1,25D-d6 administered alone or in combination with chemotherapy could be a good experimental method for accurately quantifying active 1,25D levels in cultures or in biological fluids, on both in vitro breast cancer cell lines and in vivo animal experimental models.
已经证实 1,25-二羟维生素 D3（1,25D）及其类似物具有抗肿瘤活性。氘标记的 1,25D（26,26,26,27,27,27-六氘代 1a,25-二羟维生素 D3，或 1,25D-d6）通常用作 1,25D 液相色谱-质谱（LC-MS）定量分析的内标。在本研究中，使用人乳腺癌细胞系，评估了单独给予 1,25D-d6 以及与两种常用抗肿瘤药物 5-氟尿嘧啶和依托泊苷联合应用的生物学活性。通过 MTT 测定、流式细胞术和 Western blot，我们的数据表明 1,25D-d6 对细胞增殖、细胞周期和凋亡具有与天然激素相似的作用。此外，1,25D-d6 和依托泊苷的联合使用增强了这两种化合物的抗肿瘤作用。有趣的是，这种抗肿瘤作用在侵袭性更强的 MDA-MB-231 乳腺癌细胞系中更高。我们的数据表明，单独给予 1,25D-d6 或与化疗联合使用可能是一种很好的实验方法，可用于准确定量培养物或生物流体中活性 1,25D 水平，包括体外乳腺癌细胞系和体内动物实验模型。
