Park J G, Kramer B S, Lai S L, Goldstein L J, Gazdar A F
NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20814.
J Natl Cancer Inst. 1990 Feb 7;82(3):193-8. doi: 10.1093/jnci/82.3.193.
We compared the in vitro sensitivity patterns to cytotoxic drugs and expression of the multidrug resistance-associated MDR1 gene (also known as PGY1 gene) in four gastric carcinoma cell lines with those obtained in a panel of 11 colorectal carcinoma cell lines. In addition, we tested the effects of leucovorin on enhancement of fluorinated pyrimidine-induced cytotoxicity. We used a semiautomated tetrazolium dye assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (tetrazolyl blue)] (MTT) to compare the drug sensitivity of the gastric carcinoma cell lines with that of the colorectal carcinoma cell lines. The gastric carcinoma cell lines were more sensitive to some drugs, including doxorubicin and cisplatin, but not to the fluorinated pyrimidines. Addition of leucovorin at a clinically achievable concentration enhanced the cytotoxic effects of both fluorouracil and floxuridine in colorectal carcinoma cell lines, but it enhanced the effects of only floxuridine in gastric carcinoma cell lines. With the use of a slot blot assay, relatively low levels of MDR1 RNA were present in all four gastric carcinoma cell lines, while intermediate or high levels were present in most of the colorectal carcinoma cell lines. In general, our findings reflect clinical experience and may help in the design of clinical trials.
我们比较了四种胃癌细胞系对细胞毒性药物的体外敏感性模式以及多药耐药相关的MDR1基因（也称为PGY1基因）的表达情况，与从一组11种结肠癌细胞系中获得的结果进行对比。此外，我们测试了亚叶酸对增强氟嘧啶诱导的细胞毒性的作用。我们使用半自动四唑盐染料测定法3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐（四唑蓝）来比较胃癌细胞系与结肠癌细胞系的药物敏感性。胃癌细胞系对某些药物更敏感，包括阿霉素和顺铂，但对氟嘧啶不敏感。在临床可达到的浓度下添加亚叶酸可增强结肠癌细胞系中氟尿嘧啶和氟尿苷的细胞毒性作用，但仅增强胃癌细胞系中氟尿苷的作用。通过使用斑点杂交测定法，所有四种胃癌细胞系中MDR1 RNA水平相对较低，而大多数结肠癌细胞系中存在中等或高水平。总体而言，我们的研究结果反映了临床经验，可能有助于临床试验的设计。
