Pourgholami M H, Morris D L
University of New South Wales, Department of Surgery, St. George Hospital, Kogarah, Sydney, NSW 2217, Australia.
J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):513-8. doi: 10.1016/j.jsbmb.2004.03.065.
1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2) D(3)) is a potent regulator of cell growth and differentiation, with recent evidence showing inhibition of tumor invasion, angiogenesis and tumor cell death. The growth-inhibitory properties of 1,25-(OH)(2) D(3) could be harnessed in the treatment of patients with cancer if the development of systemic hypercalcemia is avoided. Hepatocellular cancer (HCC) presents a setting where the tumor is accessible for treatment through the hepatic artery and also where the tumor is highly lipiodol avid. On this basis, we hypothesised that, 1,25-(OH)(2) D(3) dissolved in lipiodol and administered through the hepatic artery may prove to be a rational approach to the use of the drug in the treatment of HCCs. In brief, 6 years of work with 1,25-(OH)(2) D(3) at cellular, animal and clinical level has provided us with plenty of support for this hypothesis. Sensitivity of HCCs in cell culture to 1,25-(OH)(2) D(3), growth retardation of human HCC xenografts in nude mice, uptake and retention of 1,25-(OH)(2) D(3)-lipiodol by liver tumors in cell culture and animals, escalation of the 1,25-(OH)(2) D(3) dose by 100x without the development of hypercalcemia in both liver tumor bearing rats and in patients with HCC are some of the evidence that will be discussed in this paper.
1,25 - 二羟基维生素D(3)（1,25-(OH)₂D(3)）是细胞生长和分化的强效调节剂，最近有证据表明它能抑制肿瘤侵袭、血管生成并导致肿瘤细胞死亡。如果能避免全身性高钙血症的发生，1,25-(OH)₂D(3)的生长抑制特性可用于癌症患者的治疗。肝细胞癌（HCC）的情况是，肿瘤可通过肝动脉进行治疗，而且肿瘤对碘油高度亲和。基于此，我们推测，溶解于碘油并通过肝动脉给药的1,25-(OH)₂D(3)可能是治疗HCCs合理的用药方法。简而言之，在细胞、动物和临床水平上对1,25-(OH)₂D(3)进行的6年研究为这一推测提供了大量支持。HCCs在细胞培养中对1,25-(OH)₂D(3)的敏感性、人HCC异种移植瘤在裸鼠中的生长迟缓、细胞培养和动物体内肝肿瘤对1,25-(OH)₂D(3)-碘油的摄取和保留、在荷肝肿瘤大鼠和HCC患者中1,25-(OH)₂D(3)剂量增加100倍而不发生高钙血症等，都是本文将讨论的部分证据。
