放线菌素23—21对人早幼粒白血病细胞的杀伤和诱导分化

放线菌素23-21(Act23-21)对人早幼粒白血病细胞(HL-60)具有杀伤和诱导分化双重作用,其效应的强度和性质对剂量变化较敏感。采用Act23-21 5-50ng/ml处理24～72h,HL-60细胞的PC值有不同程度的降低,可低于10％,以集落形成法测得剂量—细胞存活率曲线为阈值指数型,杀伤指数达2以上。Act23-21在低浓度下(1.0～4.0ng/ml)能诱导HL-60细胞发生形态学和功能学分化,成熟细胞可达49％,细胞的分化性状能持续表达。Act23-21的诱导作用比放线菌素D(Act D)稍强,逊于二甲基亚砜(DMSO),而其诱导细胞分化性状持续表达的能力强于DMSO。

INDUCTION OF DIFFERENTIATION AND INHIBITION IN HUMAN PROMYELOID LEUKEMIA CELLS (HL-60) BY ACTINOMYCIN 23-21

Actinomycin 23-21 (Act23-21) was extrated from Streptomyces fla-veolus. This report describes tests indicating that Act23-21 is a potent inhibitor of tumours and an inducer of myeloid differentiation of human promyeloid leukemia cell line (HL-60).The antitumour activities of Act23-21 were investigated using HL-60 cell line by means of the Trypan Blue exclusion test and colony forming assay. Clonal assay suggested a dose-survival curve of threshold-exponential type contains an abruptly descending line.The human HL-60 cell line serves as a useful, more recent model of in vitro differentiation. The addition of Act23-21 for 3~5 days could, induce myeloid differentiation of HL-60 cells into morphological (as assessed on Wright-Giemsa-stained slide) and functional (as assessed by the reduce NBT dye) maturity. Cells exposed to Act 23-21 4.0ng/ml, DMSO 1.4% and Act D 4.0ng/ml for 5 days showed significant increases in the percentage of NBT-positive cells in comparison with control (44, 33, 46 with 10%, respectively).In addition,the cell differentiated characters induced by Act 23-21 could be continuous expression and the number of differentiated cells was progressively increased after washing off the, drug.