Finlay I G, Stewart G J, Pourgholami M H, Akhter J, Morris D L
University of New South Wales, Department of Surgery, St George Hospital, Kogarah, Sydney, Australia.
Anticancer Res. 2000 Jul-Aug;20(4):2705-9.
It is well established that 1, 25 dihydroxyvitamin D3 is capable of inhibiting the proliferation of a number of human cancer cell lines, including hepatoma cell lines. However, clinical usage in the treatment of cancers has been limited by its hypercalaemic effects. We hypothesised that by delivering 1, 25 dihydroxyvitamin D3 dissolved in a lipid based carrier agent as a hepatic arterial infusion it would be possible to achieve high local concentrations within hepatomas for prolonged periods, whilst avoiding high systemic concentrations and hypercalcaemia. We examined this hypothesis by administering a hepatic arterial infusion of 1, 25 dihydroxyvitamin D3 in either Lipiodol, Medium Chain Triglyceride (MCT), or saline to hepatoma bearing rats. Assay of serum and tissue concentrations revealed that this approach using lipiodol or triglyceride results in selective distribution of 1, 25-dihydroxyvitamin D3 into, and retention within hepatoma tissue and low initial systemic serum levels. Lipiodol was more effective in these respects than MCT. This method of administration has potential in the treatment of hepatoma.
众所周知，1,25-二羟基维生素D3能够抑制多种人类癌细胞系的增殖，包括肝癌细胞系。然而，其在癌症治疗中的临床应用受到高钙血症效应的限制。我们推测，通过将溶解在脂质载体中的1,25-二羟基维生素D3作为肝动脉灌注给药，有可能在肝癌组织中长时间维持高局部浓度，同时避免高全身浓度和高钙血症。我们通过向荷瘤大鼠肝动脉灌注溶解在碘油、中链甘油三酯（MCT）或盐水中的1,25-二羟基维生素D3来验证这一假设。血清和组织浓度测定表明，使用碘油或甘油三酯的这种方法可使1,25-二羟基维生素D3选择性地分布到肝癌组织中并保留在其中，且初始全身血清水平较低。在这些方面，碘油比MCT更有效。这种给药方法在肝癌治疗中具有潜力。
