In vitro search for synergy and antagonism:: evaluation of docetaxel combinations in breast cancer cell lines
In vitro search for synergy and antagonism:: evaluation of docetaxel combinations in breast cancer cell lines
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DOI：
10.1023/a:1016070230538
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发表时间：
2002-07-01
影响因子：
3.8
通讯作者：
Calabro, A
中科院分区：
文献类型：
--
作者：
Budman, DR;Calabro, A
联合化疗的使用是大多数人类恶性肿瘤的公认标准，但很少关注药物相互作用。药物的组合在细胞毒性活性方面可以是协同的、相加的或拮抗的。本研究评估了药物与多西他赛（人类乳腺癌中最活跃的药物之一）的组合，使用中位效应模型观察体外协同作用或拮抗作用作为临床结局的潜在预测因子。将三种人乳腺癌细胞系MCF 7/wt、MCF 7/adr（多重耐药）和BT 474生长至汇合，接种到96孔培养皿中，并与药物组合一起孵育72小时。MTT法检测细胞毒作用。使用中位效应分析来计算联合指数（CI），其中小于1的值表示协同作用，1表示累加效应，并且大于1表示拮抗作用。已确定的临床研究中可能有用的联合用药包括多西他赛与长春瑞滨、多西他赛与右雷佐生、多西他赛与顺式维甲酸、多西他赛与双硫仑和多柔比星或表柔比星以及多西他赛与右雷佐生和表柔比星。
The use of combination chemotherapy is the accepted standard for most human malignancies but little attention has been paid to drug interactions. A combination of drugs may be synergistic, additive, or antagonistic in cytotoxic activity. This study evaluated combinations of agents with docetaxel, one of the most active agents in human breast cancer, using a median effects model to look at synergy or antagonism in vitro as a potential predictor of clinical outcome. Three human breast cancer cell lines, MCF7/wt, MCF7/adr (multiply drug resistant), and BT474 were grown to confluence, plated into 96 well dishes, and incubated with combinations of drugs for 72 h. Cytotoxic effect was measured by the MTT assay. Median effect analysis was used to calculate the combination index (CI) with values less than 1 indicating synergism, 1 additive effects, and greater than 1 antagonism. Potentially useful combinations for clinical study which were identified included docetaxel with vinorelbine, docetaxel with dexrazoxane, docetaxel with cis-retinoic acid, docetaxel with disulfiram and either doxorubicin or epirubicin, and docetaxel with dexrazoxane and epirubicin.