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[摘要]
目的:分析常规化疗药物连续刺激对肿瘤细胞株表达erbB-2,p53和MDR1的影响,为联合应用生物治疗提供实验基础。方法: 人肺癌细胞株经ADM,VP-16,DDP单药及联合用药连续刺激,每种药物分2个剂量梯度。应用流式细胞术分别检测erbB-2,p53和MDR1的阳性细胞数及平均荧光强度,以此推算出不同药物在不同浓度下连续2~3次作用后细胞株以上各蛋白表达的细胞数、平均表达量、总表达量,同时设对照组。结果:随着培养时间的延长各项检测指标其阳性细胞的百分数、平均荧光强度及总荧光强度均呈下降趋势。高剂量各组erbB-2和MDR1以上各项指标基本上均随刺激次数的增加呈下降趋势,而低剂量各组的检测指标则有升有降;p53的表达无一定规律,但第三次刺激后药物组的表达均高于对照组。结论:化疗药物连续刺激后,特别是小剂量化疗后,erbB-2,p53和MDR1的表达可不同程度增高,提示临床上针对这些分子对病人实施生物治疗时应考虑化疗药物的影响。
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[Abstract]
Objective:To explore the variation of the proteins of erbB-2, p53 and MDR1 in repeated treatment by anticancer drugs and the effects on biotherapy. Methods:The human lung cancer cell line (LPET-a-1) was repeatedly treated by anticancer drugs—doxorubicin, etoposide, cisplatin and combination of the three drugs, and every drug was given in two concentrations. erbB-2, p53 and MDR1 were tested by flow cytometry. The percentage of cells expressing these proteins and the mean quantity of them were acquired. We could calculate the number of cells expressing each protein, the mean quantity of each protein and the total one after each treatment by different drugs in different concentration. Results:The levels of every protein decreased along with the time of cell culture. In high-dose groups, almost every item of erbB-2 and MDR1 was downregulated along with the times of treatment. In low-dose groups, there was not a rule of the item's variation and some of them increased. There was not a rule of p53 variation, and the expression of it in drug groups was higher than that in control at the third drug treatment.Conclusion:After treated by anticancer drugs, especially in low-dose, the expressions of erbB-2, p53 and MDR1 increased at different level. These data suggested that the patients suffering from cancer should be given adequate biotherapy after chemotherapy in clinical practice.
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