Etievant C, Kruczynski A, Pauwels O, Kiss R
Department de Pharmacologie Anti-cancereuse, Pierre Fabre Medicament, Castres, France.
Anticancer Res. 1991 Jan-Feb;11(1):305-11.
We assessed the in vitro drug-induced cytotoxicity by means of the rapid low-cost but weakly sensitive Thiazolyl blue (MTT) test, and the less rapid, higher cost, but highly sensitive cell image analysis (CIA) test. We studied the influence of three drugs, i.e. a vinca-alkaloid (Navelbine), an alkylating investigational agent (PE1001), and an intercalating drug, i.e. adriamycin, on the proliferation (MTT test) and cell kinetics (CIA test) of the mouse MXT and the MCF-7 mammary cancer cell lines. Adriamycin and PE1001 decreased MXT and MCF-7 cell proliferation in a dose-dependent manner as assessed by both the MTT and CIA tests. Navelbine was highly cytotoxic in a dose-dependent manner. We demonstrated that Navelbine arrests cells in the M phase without altering the G2 phase. In sharp contrast, PE1001 arrest cells in the G2 phase without altering the M phase. An adriamycin-induced effect was apparent on S phase. Thus, the MTT test allows the screening of a great number of drugs analyzed at the cell proliferation level and, in the case of MTT positive drug-induced response, the CIA test enabled the drug-induced effect at cell cycle kinetic level to be investigated.
我们通过快速、低成本但敏感性较弱的噻唑蓝（MTT）试验以及速度较慢、成本较高但敏感性高的细胞图像分析（CIA）试验评估了体外药物诱导的细胞毒性。我们研究了三种药物，即长春花生物碱（诺维本）、一种烷基化研究药物（PE1001）以及一种嵌入性药物阿霉素，对小鼠MXT和MCF-7乳腺癌细胞系增殖（MTT试验）和细胞动力学（CIA试验）的影响。通过MTT和CIA试验评估，阿霉素和PE1001均以剂量依赖方式降低了MXT和MCF-7细胞的增殖。诺维本具有高度细胞毒性，且呈剂量依赖性。我们证明，诺维本使细胞停滞于M期，而不改变G2期。与之形成鲜明对比的是，PE1001使细胞停滞于G2期，而不改变M期。阿霉素诱导的效应在S期较为明显。因此，MTT试验可用于在细胞增殖水平筛选大量药物，对于MTT试验呈阳性的药物诱导反应，CIA试验能够研究药物在细胞周期动力学水平的诱导效应。
