化疗药物对人乳腺癌细胞株MCF-7的药效动力学研究

Pharmacodynamics of chemotherapeutic drugs on MCF-7 cell line

目的 :用MTT法研究化疗药物氟尿嘧啶 ( 5 FU)、阿霉素 (ADM )、丝裂霉素 (MMC)、甲氨蝶呤 (MTX)对人乳腺癌细胞株 (MCF 7)的药效动力学特征。方法 :MCF 7细胞株在含有不同药物浓度的培养基中孵育不同时间 ,用MTT法测定细胞的抑制率。结果 :MCF 7细胞株对化疗药物的敏感性依次为ADM、5 FU、MMC ,对MTX不敏感 ,低浓度时 5 FU +ADM及 5 FU +MTX的联合用药表现了很强的协同作用 ;相同孵育时间下 ,随着药物浓度的增加 ,ADM、5 FU和MMC对MCF 7细胞株的抑制率明显增加 ,MTX的抑制率没有明显变化 ;而相同浓度下 ,在 2— 2 4h内 ,随着孵育时间的延长 ,细胞的抑制率变化不明显。计算不同作用时间时 ,相同药时曲线下面积 (AUC)的细胞抑制率 ,也呈现下降趋势。结论 :MCF 7细胞株对不同化疗药物的敏感性不同 ,化疗药物的联合应用可明显提高对细胞株的抑制率 ;在影响药剂动力学的主要因素中 ,当药物作用时间大于 2h时 。

Purpose:To improve the efficiency of chemotherapy in cancer treatment, it is useful to consider its pharmacodynamics and pharmacokinetics together. It is difficlut to study the pharmacodynamics of the chemotherapeutic drugs in vivo, so the chemotherapeutic drugs, 5 FU, ADM, MMC, MTX single and 5 FU+MTX,5 FU+ADM to MCF 7 cell line were done in vitro.Methods:The MCF 7 cell line was incubated different concentrations of the drugs for different times. Then the inhibitive rate of cell line was tested with the MTT assay. Results:DIfferences of sensitivity was found among the four drugs. In the lower concentration, marked synergy was found for 5 FU+MTX and 5 FU+ADM. The inhibitive rate of the cell line was increased markedly with increase in drug concentration as ADM, 5 FU and MCC for MCF 7 cell line, but no marked changes for MTX, The inhibition rate was not notably changed with the drugcontact time in the range of our test, 2 24 hour, and in the same condition of the same concentration for the single drug and the combined drugs. Calculating the Area of theconcentration time curve (AUC), we could find that the inbitive rate of cell line was decreasing with the time in the same value of AUC. Conclusions:THe sensitivity of MCF 7 cell line to the different drugs is variable. The combination of thechemotherapeutic drugs can produce synergy. In the factors affecting the efficienty of the chemotherapeutic drugs, the factor of drug conentration becomes the key factor when the contact time of the cell line to the drugs is longer than 2 hours.