Mogi H, Hasegawa Y, Watanabe A, Nomura F, Saka H, Shimokata K
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Cancer Chemother Pharmacol. 1997;39(3):199-204. doi: 10.1007/s002800050560.
Isobologram analysis has been widely used for evaluating the combined effect of two antitumor drugs in vitro as a pre-clinical screening test. In this study, we tried to extend two-dimensional isobologram analysis to three dimensions for evaluating the effects of a three-drug combination.
We selected three anticancer agents, cisplatin, vinorelbine and irinotecan. Each of them has been classified as having good single-agent activity against non-small-cell lung cancer (NSCLC). Human NSCLC cell lines (EBC-1, PC-3, RERF-LC-MS) were incubated for 4 days in the presence of the three drugs and cytotoxic activities were determined by a tetrazolium-based colorimetric assay (MTT assay). The data were analyzed by three dimensional isobologram analysis.
The effects of the three drugs were additive against EBC-1 (a squamous cell carcinoma cell line), subadditive against PC-3 (an adenocarcinoma cell line) and from subadditive to supraadditive against RERF-LC-MS (an adenocarcinoma cell line).
Our findings suggest that the effects of cisplatin, vinorelbine and irinotecan in combination are additive against NSCLC in vitro. These results encourage clinical trials of the three agents in combination chemotherapy for the treatment of NSCLC.
等效线图分析已被广泛用于体外评估两种抗肿瘤药物的联合作用，作为一种临床前筛选试验。在本研究中，我们试图将二维等效线图分析扩展到三维，以评估三联药物组合的效果。
我们选择了三种抗癌药物，顺铂、长春瑞滨和伊立替康。它们每种都被归类为对非小细胞肺癌（NSCLC）具有良好的单药活性。人NSCLC细胞系（EBC-1、PC-3、RERF-LC-MS）在三种药物存在的情况下培养4天，并通过基于四唑盐的比色法（MTT法）测定细胞毒性活性。数据通过三维等效线图分析进行分析。
这三种药物对EBC-1（一种鳞状细胞癌细胞系）的作用是相加的，对PC-3（一种腺癌细胞系）的作用是次相加的，对RERF-LC-MS（一种腺癌细胞系）的作用从次相加到超相加。
我们的研究结果表明，顺铂、长春瑞滨和伊立替康联合使用在体外对NSCLC的作用是相加的。这些结果鼓励对这三种药物进行联合化疗治疗NSCLC的临床试验。
