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体外药物诱导细胞毒性的不均匀性,表现为 IC 值的差异 - 影响和前进方向。

Non-uniformity in in vitro drug-induced cytotoxicity as evidenced by differences in IC values - implications and way forward.

机构信息

Department of Human Genetics, Faculty of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu 600116, India.

Department of Biotechnology, Anna University, Guindy, Chennai 600 025, India.

出版信息

J Pharmacol Toxicol Methods. 2023 Jan-Feb;119:107238. doi: 10.1016/j.vascn.2022.107238. Epub 2022 Dec 12.

Abstract

Cell lines have proven indispensable for in vitro experiments and their utility as experimental models range from understanding the fundamental cell functioning to drug discovery. One of the most common utility of cell lines is for in vitro drug testing. Drug testing involves determining the cytotoxic effects of the drugs and such a measurement is expressed as the IC values of drugs. Although determination of IC values of drugs on cell lines is one of the most common in vitro experimental approaches, a significant amount of variations can be observed in the results obtained from such studies. Although the variations in the IC values of a drug on different cells lines can and should vary, the non-uniformity of such results reported from different studies using a particular drug on a specific cell line is a matter of concern. We present the IC values of 5 most commonly used drugs 5-fluorouracil, bleomycin, cisplatin, doxorubicin and methotrexate obtained from several in vitro cell line-based studies. Some of the factors which contribute to the non-uniformity of the IC values for a particular drug from different studies are discussed as three types of factors, the biological, non-biological and human factors. Also, ways in which such variations can be reduced to obtain universally common, reliable results are presented.

摘要

细胞系已被证明在体外实验中不可或缺,其用途广泛,从理解基本细胞功能到药物发现。细胞系最常见的用途之一是用于体外药物测试。药物测试包括确定药物的细胞毒性作用,此类测量以药物的 IC 值表示。尽管确定细胞系上药物的 IC 值是最常见的体外实验方法之一,但从这些研究中获得的结果会存在很大差异。尽管不同细胞系上药物的 IC 值变化可以而且应该有所不同,但使用特定药物在特定细胞系上的不同研究报告的结果不一致仍然令人担忧。我们提供了来自多个基于细胞系的体外研究中获得的 5-氟尿嘧啶、博来霉素、顺铂、多柔比星和甲氨蝶呤这 5 种最常用药物的 IC 值。讨论了导致不同研究中特定药物的 IC 值不一致的一些因素,分为生物因素、非生物因素和人为因素这 3 种类型。还介绍了如何减少这些差异以获得普遍适用、可靠的结果。

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