Ulukaya Engin, Ozdikicioglu Ferda, Oral Arzu Yilmaztepe, Demirci Meral
Biochemistry and Clinical Chemistry Department, Medical School of Uludag University, 16059 Gorukle, Bursa, Turkey.
Toxicol In Vitro. 2008 Feb;22(1):232-9. doi: 10.1016/j.tiv.2007.08.006. Epub 2007 Aug 23.
Accurate assessment of the anti-growth effects of chemotherapeutics is immensely importance in cancer research with regard to drug discovery and toxicological safety. A number of in vitro cytotoxicity assays are used for these purposes. However, there is the possibility for different results in the assessments because the way they measure the viability of cancer cells is specific to each assay. In the present study, the performance of two common assays (MTT and ATP) in the assessment of anti-growth effects of chemotherapeutics on a lung cancer cell line (A549) was compared. The cells were treated with paclitaxel, docetaxel, gemcitabine, 5-fluorouracil (5-FU), etoposide, doxorubicin, epirubicin, cisplatin, 4-hydroperoxycyclophosphamide (4-HC) and carboplatin in six different concentrations. When taking all the drugs and inhibitions into account, a moderate correlation (r=0.670; p=0.01) between the assays was found. However, IC 50 values by the MTT assay were higher in 90% of the drugs than those found by the ATP assay. In addition to this, there was a statistically significant difference between the dose response curves of the assays, which was dependent on the drugs of choice. We recommend caution in comparing these assays to evaluate the anti-growth effects of chemotherapeutics because the MTT assay seem to give rise to relatively lower inhibition (higher viability) levels than the ATP assay, depending on the drugs of choice.
在癌症研究中,对于药物发现和毒理学安全性而言,准确评估化疗药物的抗生长作用极为重要。许多体外细胞毒性试验用于这些目的。然而,由于它们测量癌细胞活力的方式因每种试验而异,评估结果可能会有所不同。在本研究中,比较了两种常用试验(MTT和ATP)在评估化疗药物对肺癌细胞系(A549)的抗生长作用方面的性能。用六种不同浓度的紫杉醇、多西他赛、吉西他滨、5-氟尿嘧啶(5-FU)、依托泊苷、阿霉素、表阿霉素、顺铂、4-氢过氧环磷酰胺(4-HC)和卡铂处理细胞。综合考虑所有药物和抑制作用,发现两种试验之间存在中等程度的相关性(r = 0.670;p = 0.01)。然而,MTT试验测得的90%药物的IC50值高于ATP试验测得的值。除此之外,两种试验的剂量反应曲线之间存在统计学上的显著差异,这取决于所选择的药物。我们建议在比较这些试验以评估化疗药物的抗生长作用时要谨慎,因为根据所选择的药物不同,MTT试验似乎比ATP试验产生相对较低的抑制(较高的活力)水平。