抗三尖杉酯碱HL－60细胞的抗程序性细胞死亡及其克服  

APOPToSIS RESISTANCE AND ITS REVERSAL IN HARRINGTONINE RESISTANT CELL LINE*

作　　者：方敏[1] 张鸿卿[1] 薛绍白[1] 庞大本[1] 池旭生[1] 

机构地区：[1]北京师范大学生物系,中国中医研究院

出　　处：《药学学报》1994年第12期891-898,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金和国家教委博士点基金

摘　　要：三尖杉酯碱（ｈａｒｒｉｎｇｔｏｎｉｎ，ＨＴ）是中国产植物海南粗榧（ＣｅｐｈａｌｏｔａｘｕｓｈａｉｎａｎｅｎｓｉｓＬｉ）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。Harringtonine(HT),a domestic antitumor drug extracted from Cephalotaxushainanensis 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.

关 键 词：抗癌药 细胞死亡 三尖杉酯碱 人白血病细胞 

分 类 号：R979.1[医药卫生—药品]