抗三尖杉酯碱HL-60细胞的抗程序性细胞死亡及其克服

三尖杉酯碱(harringtonin,HT)是中国产植物海南粗榧(Cephalotaxus hainanensis Li)中提取的一种抗肿瘤药物,对急性粒细胞白血病、急性单核细胞白血病有较好疗效⁽¹⁾。三尖杉酯碱可非常有效地诱导敏感HL-60细胞程序性死亡(apoptosis,Apo)^(2,3)。但超过半致死剂量(IC₅₀)近百倍的HT却不能诱导抗三尖杉酯碱细胞HT12程序性死亡。如用维拉帕米(verapamil,Vp)10μg·mL^-1逆转多药抗性后,HT虽可诱导HT12细胞程序性死亡,但与敏感细胞相比,出现程序性细胞死亡的时间大大推迟,用药浓度也提高约10倍。这些结果提示:程序性细胞死亡可能作为肿瘤细胞是否已形成抗药性的标志之一,同时也说明程序性细胞死亡相关因子可能参与肿瘤细胞抗药性的形成。

APOPTOSIS RESISTANCE AND ITS REVERSAL IN HARRINGTONINE RESISTANT CELL LINE

Harringtonine(HT),a domestic antitumor drug extracted from Cephalotaxus hainanensis Li showed high chemotherapeutic efficacy on human acute granulocytic leukemia and acutemyelocytic leukemia in clinics.Apoptosis of HL-60 cells can be induced by HT effectively; but forcells resistant to harringtonine,apoptosis can not be induced, even if the drug(HT)concentration isover 100 times of IC₅₀0 value. Although apoptosis occurred when its multidrugs resistance had beenreversed by verapamil, compared with sensitive HL-60 cells, the time at which apoptosis happeneddelaved and the drug dosage increased. All these suggest that apoptotic resistance might be one of themarks of drug resistance in tumor cells, and apoptosis related factors could play a role in the formation of multidrug resistance.