Ollikainen T, Knuuttila A, Suhonen S, Taavitsainen M, Jekunen A, Mattson K, Linnainmaa K
Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki.
Anticancer Drugs. 2000 Feb;11(2):93-9. doi: 10.1097/00001813-200002000-00005.
In this study, we used four human mesothelioma cell lines (M14K, M24K, M25K and M38K), one transformed human mesothelial cell line (MeT-5A) and one primary mesothelial culture (UPL) to test for in vitro sensitivity to docetaxel, paclitaxel, SN-38 [an active metabolite of irinotecan (CPT-11)] and gemcitabine, as single agents. Subconfluent cell cultures were treated with 2x10(-9), 5x10(-9), 10(-8), 2x10(-8) and 5x10(-8) M concentrations of each drug for 48 h. The sensitivity was measured in terms of cell viability using the Trypan blue exclusion method. All four drugs were potent inhibitors of mesothelioma cell growth, but cell lines from different patients diverged in their sensitivity to the individual agents. In most cases docetaxel, paclitaxel and SN-38 were more potent killers of mesothelioma cells than gemcitabine. The induction of DNA damage was investigated using the Comet assay; cells from two cell lines (M14K and M25K) were treated with subtoxic 10(-8) M concentrations of each drug for 4, 24 and 48 h. Each of the agents caused a slight increase in DNA single-strand breaks at a concentration of 10(-8) M.
在本研究中，我们使用了四种人恶性间皮瘤细胞系（M14K、M24K、M25K和M38K）、一种转化的人胸膜间皮细胞系（MeT-5A）和一种原代胸膜间皮细胞培养物（UPL），以测试它们对多西他赛、紫杉醇、SN-38[伊立替康（CPT-11）的活性代谢物]和吉西他滨作为单一药物的体外敏感性。将亚汇合细胞培养物用每种药物的2×10⁻⁹、5×10⁻⁹、10⁻⁸、2×10⁻⁸和5×10⁻⁸M浓度处理48小时。使用台盼蓝排斥法根据细胞活力来测量敏感性。所有四种药物都是恶性间皮瘤细胞生长的有效抑制剂，但来自不同患者的细胞系对各个药物的敏感性存在差异。在大多数情况下，多西他赛、紫杉醇和SN-38对恶性间皮瘤细胞的杀伤作用比吉西他滨更强。使用彗星试验研究DNA损伤的诱导情况；来自两种细胞系（M14K和M25K）的细胞用每种药物的亚毒性10⁻⁸M浓度处理4、24和48小时。在10⁻⁸M浓度下，每种药物都导致DNA单链断裂略有增加。
