Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay.
Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay.
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发表时间：
1988-02
期刊：
影响因子：
11.2
通讯作者：
M. Alley;Dominic A. Scudiere;A. Monks;M. Hursey;M. Czerwiński;D. Fine;B. Abbott;J. Mayo;R. Sh
中科院分区：
文献类型：
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作者：
M. Alley;Dominic A. Scudiere;A. Monks;M. Hursey;M. Czerwiński;D. Fine;B. Abbott;J. Mayo;R. Sh
在过去的30年里，潜在抗癌药物的临床前发现和开发策略主要基于对携带可移植白血病和来自有限数量的小鼠和人类来源的实体瘤的小鼠的药物测试。实施另一种方法的可行性正在研究中，即在体外/体内联合筛选来自广泛人类实体肿瘤的人类肿瘤细胞系小组中的选择性细胞毒性。从不同来源获得的代表8种肺癌病理的30种细胞系以及代表其他10种人类癌症(结肠癌、乳腺癌、肾癌、前列腺癌、卵巢癌、头颈癌、胶质瘤、白血病、黑色素瘤和肉瘤)的76种细胞株在单一的标准培养基中表现出可接受的生长特征和合适的比色曲线。细胞介导的四唑盐还原法测定微培养孔中的体外生长与贴壁细胞系培养的细胞蛋白测定和悬浮细胞系培养的活细胞数(0.94小于R2小于0.99)具有很好的相关性(0.89小于R2小于0.98)。由于微培养四唑盐试验提供了敏感和可重复性的生长指标，以及单个细胞系在多代和几个月的培养过程中的药物敏感性，它似乎适合于体外药物筛选的初期阶段。
For the past 30 years strategies for the preclinical discovery and development of potential anticancer agents have been based largely upon the testing of agents in mice bearing transplantable leukemias and solid tumors derived from a limited number of murine as well as human sources. The feasibility of implementing an alternate approach, namely combined in vitro/in vivo screening for selective cytotoxicity among panels of human tumor cell lines derived from a broad spectrum of human solid tumors is under investigation. A group of 30 cell lines acquired from a variety of sources and representing 8 lung cancer pathologies as well as 76 cell lines representing 10 other categories of human cancer (carcinomas of colon, breast, kidney, prostate, ovary, head and neck; glioma; leukemia; melanoma; and sarcoma) have exhibited acceptable growth characteristics and suitable colorimetric profiles in a single, standard culture medium. Measurements of in vitro growth in microculture wells by cell-mediated reduction of tetrazolium showed excellent correlation (0.89 less than r2 less than 0.98) with measurements of cellular protein in adherent cell line cultures as well as viable cell count in suspension cell line cultures (0.94 less than r2 less than 0.99). Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening.