Scott & White Digestive Disease Research Center, Scott & White, Texas A&M Health Science Center, College of Medicine, Temple, TX, USA.
Dig Liver Dis. 2013 Apr;45(4):316-22. doi: 10.1016/j.dld.2012.12.012. Epub 2013 Feb 1.
Cholangiocarcinoma is a deadly biliary tumour with limited treatment strategies. Vitamin (1,25(OH)2D) has anti-proliferative effects on several cancers. Vitamin D3 is synthesized by the enzyme, CYP27B1, and signals via the nuclear vitamin D3 receptor. The enzyme, CYP24A1, degrades vitamin D3.
(i) Measure the expression of CYP27B1, CYP24A1, and vitamin D3 receptor in human nonmalignant and cholangiocarcinoma lines and biopsy control or tumour samples; and (ii) evaluate the effects of vitamin D3 on vitamin D3 synthesis and cholangiocarcinoma growth.
In vitro studies were performed in malignant and nonmalignant cholangiocytes. Vitamin D3 receptor, CYP24 and CYP27 expression was measured in cell lines and biopsy samples. Cell lines were stimulated with vehicle or vitamin D3 from 30min to 48h. Cell viability was assessed by MTS assays and BrdU incorporation. Vitamin D3 receptor, CYP24A1 and CYP27B1 expression was measured in cholangiocarcinoma cells stimulated with vehicle or vitamin D3.
In cholangiocarcinoma lines and biopsy samples, vitamin D3 receptor and CYP24A1 expression increased compared to controls, whereas CYP27B1 expression was decreased or unchanged. Vitamin D3 induced nuclear translocation of vitamin D3 receptor in cholangiocarcinoma and decreased cholangiocarcinoma growth.
Treatment with vitamin D3 decreased CYP24A1, whereas CYP27B1 expression increased. Modulation of vitamin D3 synthesis may be important in the management of cholangiocarcinoma.
胆管癌是一种致命的胆道肿瘤，治疗策略有限。维生素（1,25(OH)2D）对多种癌症具有抗增殖作用。维生素 D3 由酶 CYP27B1 合成，并通过核维生素 D3 受体发出信号。酶 CYP24A1 降解维生素 D3。
（i）测量人非恶性和胆管癌细胞系和活检对照或肿瘤样本中 CYP27B1、CYP24A1 和维生素 D3 受体的表达；（ii）评估维生素 D3 对维生素 D3 合成和胆管癌生长的影响。
在恶性和非恶性胆管细胞中进行体外研究。在细胞系和活检样本中测量维生素 D3 受体、CYP24 和 CYP27 的表达。细胞系用载体或维生素 D3 刺激 30 分钟至 48 小时。通过 MTS 测定和 BrdU 掺入评估细胞活力。用载体或维生素 D3 刺激胆管癌细胞后测量维生素 D3 受体、CYP24A1 和 CYP27B1 的表达。
与对照相比，胆管癌细胞系和活检样本中的维生素 D3 受体和 CYP24A1 表达增加，而 CYP27B1 表达减少或不变。维生素 D3 诱导胆管癌细胞中维生素 D3 受体的核易位，并降低胆管癌细胞的生长。
维生素 D3 的治疗降低了 CYP24A1 的表达，而 CYP27B1 的表达增加。维生素 D3 合成的调节可能在胆管癌的治疗中很重要。
