Colston K W, Mackay A G, James S Y, Binderup L, Chander S, Coombes R C
Department of Clinical Biochemistry, St Georges Hospital Medical School, Tooting, London, U.K.
Biochem Pharmacol. 1992 Dec 15;44(12):2273-80. doi: 10.1016/0006-2952(92)90669-a.
EB1089 is a novel vitamin D analogue which has been tested for its effects on breast cancer cell growth in vitro, using the established human breast cancer cell line MCF-7, and in vivo on the growth of established rat mammary tumours. Both EB1089 and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) inhibited MCF-7 cell proliferation with the synthetic analogue being at least an order of magnitude more potent than the native hormone. In vivo anti-tumour effects were investigated using the N-methyl-nitrosourea-induced rat mammary tumour model. Oral treatment with EB1089 was tested at three doses. With the lower dose, significant inhibition of tumour growth was seen in the absence of a rise in serum calcium. The same dose of 1,25-(OH)2D3 had no effect on tumour growth but caused hypercalcaemia. With the higher dose of EB1089, striking tumour regression was seen although serum calcium rose. This report demonstrates that EB1089 possess enhanced anti-tumour activity coupled with reduced calcaemic effects relative to 1,25-(OH)2D3 and thus may have therapeutic potential as an anti-tumour agent.
EB1089是一种新型维生素D类似物,已对其在体外对人乳腺癌细胞生长的影响进行了测试,使用的是已建立的人乳腺癌细胞系MCF-7,并且在体内对已形成的大鼠乳腺肿瘤的生长进行了测试。EB1089和1,25-二羟基维生素D3(1,25-(OH)2D3)均抑制MCF-7细胞增殖,这种合成类似物的效力比天然激素至少高一个数量级。使用N-甲基亚硝基脲诱导的大鼠乳腺肿瘤模型研究了体内抗肿瘤作用。对EB1089进行了三种剂量的口服治疗测试。较低剂量时,在血清钙未升高的情况下观察到肿瘤生长受到显著抑制。相同剂量的1,25-(OH)2D3对肿瘤生长没有影响,但导致了高钙血症。较高剂量的EB1089时,尽管血清钙升高,但仍观察到显著的肿瘤消退。本报告表明,相对于1,25-(OH)2D3,EB1089具有增强的抗肿瘤活性以及降低的血钙效应,因此可能具有作为抗肿瘤药物的治疗潜力。