Doré B T, Chomienne C, Momparler R L
Département de pharmacologie, Université de Montréal, Québec, Canada.
Cancer Chemother Pharmacol. 1998;41(4):275-80. doi: 10.1007/s002800050740.
The object of this study was to investigate the antineoplastic action of 5-aza-2'-deoxycytidine (5-AZA) in combination with vitamin D analogs on HL-60 and NB-4 myeloid leukemic cells. The vitamin D analogs chosen for this investigation were 1,25-(OH)2-23-yne-cholecalciferol (23-D) and 1,25-(OH)2-delta16-23-yne-cholecalciferol (16-23-D) since they have the potential to be used clinically owing to their minimal action on calcium metabolism.
HL-60 and NB-4 leukemic cells were incubated with different concentrations of 5-AZA and either 23-D or 16-23-D and their antineoplastic action determined by inhibition of DNA synthesis and growth, induction of differentiation and colony assay.
5-AZA in combination with either vitamin D analog produced a greater growth inhibition and induction of differentiation than either agent alone. For HL-60 leukemic cells the combination of 5-AZA with either analog produced a synergistic loss of clonogenicity. These effects on clonogenicity correlated with the effects of the combination on inhibition of growth and DNA synthesis.
These results suggest that vitamin D analogs may enhance the antileukemic action of 5-AZA and that it may be interesting to test these agents in combination in patients with myeloid leukemia.
本研究旨在探讨5-氮杂-2'-脱氧胞苷（5-AZA）与维生素D类似物联合应用对HL-60和NB-4髓系白血病细胞的抗肿瘤作用。本研究选用的维生素D类似物为1,25-(OH)2-23-炔胆钙化醇（23-D）和1,25-(OH)2-Δ16-23-炔胆钙化醇（16-23-D），因为它们对钙代谢的影响极小，具有临床应用潜力。
将HL-60和NB-4白血病细胞与不同浓度的5-AZA以及23-D或16-23-D一起孵育，通过抑制DNA合成和生长、诱导分化以及集落测定来确定它们的抗肿瘤作用。
5-AZA与任何一种维生素D类似物联合应用时，所产生的生长抑制和分化诱导作用均比单独使用任何一种药物时更强。对于HL-60白血病细胞，5-AZA与任何一种类似物联合应用都会导致克隆形成能力协同丧失。这些对克隆形成能力的影响与联合用药对生长和DNA合成的抑制作用相关。
这些结果表明，维生素D类似物可能会增强5-AZA的抗白血病作用，并且在髓系白血病患者中联合测试这些药物可能会很有意义。
