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顺铂的耐药性存在多种机制 ,包括顺铂蓄积降低、谷胱甘肽 ( GSH)和金属硫蛋白水平增加、DNA修复增强等。凋亡过程中致癌基因的表达和信号转导通路的改变也与顺铂的耐药性有关。在这些机制中 ,顺铂蓄积降低最常见。使用 DNA修复抑制剂及能增加顺铂蓄积和降低 GSH的药物可增加对顺铂的敏感性 ,但是 ,所试验的药物均不能完全逆转顺铂的耐药性。这表明 ,体外试验中同一细胞系中产生了多种耐药机制。
There are many mechanisms of cisplatin resistance, including decreased cisplatin accumulation, increased levels of glutathione (GSH) and metallothionein, and enhanced DNA repair. Changes in the expression of oncogenes and signal transduction pathways during apoptosis are also associated with cisplatin resistance. Among these mechanisms, the decrease in cisplatin accumulation is most common. The use of DNA repair inhibitors and drugs that increase cisplatin accumulation and decrease GSH may increase susceptibility to cisplatin. However, none of the tested drugs completely reverses the resistance of cisplatin. This indicates that multiple drug resistance mechanisms have been generated in the same cell line in vitro.