肿瘤细胞的抗药性是肿瘤化疗失败的主要原因。探讨抗药性机制和克服抗药性的途径是肿瘤化疗的重大课题。几乎所有的抗癌药物在长期使用后都会诱发产生抗性。抗药性不仅与细胞本身的生理机制有关，而且也证明与细胞的增殖、分化和癌变密切相关。 HL-60细施是体外研究白血病和分化的模型。兰尖衫酯碱是一种对白血病有明显疗效的抗癌药。HL-60/Har是我室从对三尖杉酯碱繁感的HL-80细胞中筛选出的抗三尖杉酯碱的多药抗性细胞模型。 本文以HL-60和HL-60/Har细胞为模型，比较了两者在某些性质上的差异，以探讨抗药性产生的机理。维甲酸是治疗白血病十分有效的分化诱导剂，在临床上已得到广泛应用。本文比较了HL-60/Har和HL-60细胞对维甲酸的不同反应，试图探讨坑药性与诱导分化的关系。初步得出从下结论： 一.HL-60/Har细胞脱药培养一年半，抗性倍数稳定在20倍左右。 二.HL-60/Har细胞的倍增时间为29小时，HL-60细胞的倍增时间为24小时，HL-SO/Har的倍增时间较HL-60长。 三.HL-60/Har总的PKC活性是68cpm/ng蛋白，HL-60总的PKC活性是34cpm/μg蛋白，HL-60/Har总的化C活性较HL-60细胞高。 四.HL-60/Har的集落形成率是26%，HL-60细胞是52%，HL-60/Har的集落形成率低于HL-60细胞。 五.HL-60/Har细胞中c-fos、c-myc基因的表达都较HL-60细胞中的低。 六.HL-60/Har细胞对维甲酸的细胞毒作用有抗性，抗性倍数三倍。 七.用lμM维甲酸分别诱导HL-60和HL-60/Har72小时，分化率分别为88%和32%，HL-60/Har对维甲酸的诱导分化有抗性。 八.在lμM维甲酸分别诱导HL-60和HL-60/Har72小时，分别测得单细胞内钙离子浓度和活化钙调素含量，发现诱导分化后细胞內钙离子浓度升高、活化钙调素含量下降。

Emergence of drug resistance in tumor cells is believed to be a major cause for failure of cancer chemotherapy. The investigations on the mechanisms of multidrug resistance have become a major subject of tumor chemotherapy. Almost all the antitumor drugs can induce resistance when they are used for a long time. Drug resistance related not only to the physiological mechanisms of cell itself, but also to the cell proliferation,differentiation and carcinogenesis. Harringtonine is an antitumor drug which has evident curative effecton leukemia. HL-60 cell line is the model used in studying leukemia and differentiation in vitro. HL-60/Har cell is a harringtonine-resistant variant of the HL-60 human leukemia cell line, which demonstrates multidrug resistance. To explore the mechanism of drug resistance, we compared the characterization of HL-60 and HL-60/Har ce11s.Al1 trans retinoic acid is an effective differentiation inducer and ts clinical pratice is taken seriously and widely. To investigate the relations between drug- resistance and induced differentiation, we compared the different reactions of HL-60 and HL-60/Har cells to all trans retinoic acid. The preiiminary conciusions are as following: 1. Though HL-60/Har cells had been cultivated without harringtonine for one and half year, it's resistance about 20-fold to harringtonine is stable. 2. The doubling time of HL-60/Har cells is 29 hours but that of HL-60 cells is 24 hours. 3. The total PKC activity of HL-80/Har cells is almost 2- fold that of HL-60 cells. 4. The colony forming of HL-60/Har cells is lower than that of HL-60 cells. HL-60/Har's colony forming is half of HL-60 ce11s. 5. The expression of c-fos and c-myc in HL-60/Har cells is lower than that in HL-60 cells. 6. HL-60/Har cells acquired 3-fold resistance to all trans- retinoic acid's cytotoxity. 7. Cultivated with 1 um RA after 72 hours, HL- 80/Har cells were induced to differentiate with NBT positive percentage 32%, but that of HL-60 cells were 88%.HL-60/Har cells also acquired resistance to RA's differentiation induction. 8. Our results demonstrated that, after exposure to RA for 72 hoursdifferentiated cells'intracellular free calcium concentration increased, while calcium activated calmodulin contents decreased.