Department of Biostatistics and Biomedical Systems Theory, Faculty of Pharmacy, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Toruń, Jagiellońska Str. 15, 87-067 Bydgoszcz, Poland.
Department of Immunology, Faculty of Pharmacy, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Toruń, M. Curie-Sklodowska Str. 9, 85-094 Bydgoszcz, Poland.
Molecules. 2023 Jul 30;28(15):5761. doi: 10.3390/molecules28155761.
Cisplatin is a classic anticancer drug widely used as a reference drug to test new metal complex drug candidates. We found an unexpected diversity in cisplatin-related cytotoxicity values, expressed as IC (the half-maximal inhibitory concentration) in tumour cell lines, such as MCF-7, HepG2 and HeLa. We reviewed the data published from 2018 to 2022. A total of 41 articles based on 56 in vitro experiments met our eligibility criteria. Using a meta-analysis based on a random effect model, we evaluated the cytotoxicity of cisplatin (IC) after 48- or 72-h cell exposure. We found large differences between studies using a particular cell line. According to the random effect model, the 95% confidence intervals for IC were extremely wide. The heterogeneity of cisplatin IC, as measured by the I index for all cancer cell lines, was over 99.7% at culture times of 48 or 72 h. Therefore, the variability between studies is due to experimental heterogeneity rather than chance. Despite the higher IC values after 48 h than after 72 h, the heterogeneity between the two culture periods did not differ significantly. This indicates that the duration of cultivation is not the main cause of heterogeneity. Therefore, the available data is diverse and not useful as a reference. We discuss possible reasons for the IC heterogeneity and advise researchers to conduct preliminary testing before starting experiments and not to solely rely on the published data. We hope that this systematic meta-analysis will provide valuable information for researchers searching for new cancer drugs using cisplatin as a reference drug.
顺铂是一种经典的抗癌药物,被广泛用作测试新金属络合物候选药物的参考药物。我们发现顺铂相关细胞毒性值存在出乎意料的多样性,以 MCF-7、HepG2 和 HeLa 等肿瘤细胞系中的 IC(半最大抑制浓度)表示。我们回顾了 2018 年至 2022 年发表的数据。共有 41 篇基于 56 项体外实验的文章符合我们的入选标准。我们使用基于随机效应模型的荟萃分析评估了 48 或 72 小时细胞暴露后顺铂的细胞毒性(IC)。我们发现使用特定细胞系的研究之间存在很大差异。根据随机效应模型,IC 的 95%置信区间非常宽。所有癌细胞系的 I 指数测量的顺铂 IC 的异质性在 48 或 72 小时培养时超过 99.7%。因此,研究之间的变异性是由于实验异质性而不是偶然。尽管 48 小时后的 IC 值高于 72 小时,但两个培养期之间的异质性没有显著差异。这表明培养时间不是异质性的主要原因。因此,现有数据是多样化的,不能作为参考。我们讨论了 IC 异质性的可能原因,并建议研究人员在开始实验前进行初步测试,而不要仅依赖已发表的数据。我们希望本系统的荟萃分析能为使用顺铂作为参考药物寻找新抗癌药物的研究人员提供有价值的信息。