目的: 研究胸苷酸合成酶抑制剂ZD 1694体外抗肿瘤活性.方法:采用MTT比色法测定8种肿瘤细胞株(神经胶质瘤细胞株、肝癌细胞株、乳腺癌细胞株、胃腺癌细胞株、宫颈癌细胞株、急性髓细胞性白血病细胞株、急性早幼粒细胞白血病细胞株和卵巢癌细胞株)分别对ZD 1694和氟尿嘧啶的敏感性,每种药物设定6个浓度等级,分别是Cmax×100,Cmax×10,Cmax×1,Cmax×0.1,Cmax×0.01,和Cmax×0.001.结果:ZD 1694和氟尿嘧啶对8种肿瘤细胞72 h的生长抑制均呈浓度依赖性增加,ZD 1694对SK-N-SH(神经胶质瘤细胞株),K 562(急性髓细胞性白血病细胞株),Bcap-37(乳腺癌细胞株),HELA(宫颈癌细胞株)和HL-60(急性早幼粒细胞白血病细胞株)5种肿瘤细胞的IC50分别为0.4,0.6,2.2,3.2和0.2 μmol·L-1,氟尿嘧啶对SK-N-SH(神经胶质瘤细胞株),K-562(急性髓细胞性白血病细胞株),Bcap-37(乳腺癌细胞株),SGC-7901(胃腺癌细胞株)和HO 8910(卵巢癌细胞株)5种肿瘤细胞的IC50分别为5.5,253.7,150.7,161.7和371.3 μmol·L-1,这8种肿瘤细胞对ZD 1694和氟尿嘧啶的敏感程度分别为62.5 %和12.5 %.结论:ZD 1694和氟尿嘧啶都能浓度依赖性地抑制多种肿瘤细胞的增殖,同时ZD 1694较氟尿嘧啶具有更高的抗肿瘤活性.%AIM: To investigate the effects of the thymidylate synthase(TS) inhibitor-ZD 1694 against cancer cell lines in vitro. METHODS: The in vitro growth inhibition of eight human cancer cell lines (carcinoma of neuroglioma, liver, breast, gastric gland, cervix, acute myelocytic leukemia, acute promyelocytic leukemia and ovary) of ZD 1694 and fluorouracil (5-FU) using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium blue (MTT) colorimetric assay were tested. The concentrations of drugs were Cmax×100, Cmax×10, Cmax×1,Cmax×0.1, Cmax×0.01, and Cmax×0.001, respectively. RESULTS: Inhibition of growth of the eight cancer cell lines by ZD 1694 and 5-FU was concentration-dependent following 72 h exposure to the two drugs. 50 % inhibiting concentration (IC50) of ZD 1694 to SK-N-SH, K-562, Bcap-37, HELA and HL-60 was 0.4, 0.6, 2.2, 3.2, and 0.2 μmol*L-1, respectively. IC50 of 5-FU to SK-N-SH, K-562, Bcap-37, SGC-7901 and HO-8910 was 5.5, 253.7, 150.7, 161.7, and 371.3 μmol*L-1, respectively. Efficacy rate of these eight cancer cells to ZD 1694 and 5-FU was 62.5 % and 12.5 %, respectively. CONCLUSION: ZD 1694 and 5-FU both inhibit growth of various malignancies, respectively. Compared with 5-FU, ZD 1694 is more effective on these eight cancer cells.
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