Jamali Bardia, Nakhjavani Maryam, Hosseinzadeh Leila, Amidi Salimeh, Nikounezhad Nastaran, H Shirazi Farshad
Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Toxicology and Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2015 Spring;14(2):513-9.
One of the major complications in cancer chemotherapy with cisplatin as one of the important medicines in treatment regimens of different cancers is the development of resistance. One of the most described cellular defense mechanisms involved in resistance is glutathione (GSH), thus in this study, the effects of cisplatin on the total intracellular GSH level (GSHi) in some sensitive and resistant variants of human cell lines (hepatocarcinoma HepG2, skin A375, cisplatin sensitive glioblastoma U373MG and cisplatin resistant glioblastoma U373MGCP, cisplatin sensitive ovary A2780S and cisplatin resistant A2780CP cells) were studied. MTT assay was performed to measure cytotoxicity of cisplatin (33.3 µM for 1 hour). Following cisplatin exposure, GSHi (per million cells) was evaluated using a photometrical assay up to 90 minutes. Our results indicate that there are significant differences between GSHi content of A2780CP and U373MGCP cells compared to other cell lines. Moreover, IC50 of cisplatin in different cells seems to have a relation with mean of GSH level in 90 minutes (GSH (mean)90). As a conclusion, it seems that resistance to cisplatin in different cell lines is more related with the diverse patterns of GSHi variations following cisplatin exposure than its original level, and/or its cellular increase or decrease. It is also suggested that GSH (mean)90 may be used as a factor for the prediction of cellular resistance to cisplatin.
顺铂作为不同癌症治疗方案中的重要药物之一，其在癌症化疗中的主要并发症之一是耐药性的产生。在耐药性中最常被描述的细胞防御机制之一是谷胱甘肽（GSH），因此在本研究中，研究了顺铂对一些人类细胞系敏感和耐药变体（肝癌HepG2、皮肤癌A375、顺铂敏感的胶质母细胞瘤U373MG和顺铂耐药的胶质母细胞瘤U373MGCP、顺铂敏感的卵巢癌A2780S和顺铂耐药的A2780CP细胞）中细胞内总谷胱甘肽水平（GSHi）的影响。进行MTT试验以测量顺铂（33.3μM，作用1小时）的细胞毒性。顺铂暴露后，使用光度法测定法评估长达90分钟的GSHi（每百万细胞）。我们的结果表明，与其他细胞系相比，A2780CP和U373MGCP细胞的GSHi含量存在显著差异。此外，顺铂在不同细胞中的IC50似乎与90分钟时的谷胱甘肽水平平均值（GSH（平均值）90）有关。总之，不同细胞系对顺铂的耐药性似乎与其在顺铂暴露后GSHi变化的不同模式更为相关，而非其原始水平和/或细胞内的增加或减少。还建议GSH（平均值）90可作为预测细胞对顺铂耐药性的一个因素。
