Scanlon K J, Wang W Z, Han H
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010.
Cancer Treat Rev. 1990 Dec;17 Suppl A:27-35. doi: 10.1016/0305-7372(90)90013-6.
Most cancer chemotherapeutic agents are designed to damage DNA directly or indirectly. One mechanism of cellular resistance to these agents is enhanced DNA repair. Human ovarian carcinoma cells resistant to cisplatin (A2780DDP) respond to cisplatin treatment with a 3-6-fold increase in gene expression for oncogenes, DNA repair enzymes and enzymes necessary for the synthesis of thymidine. Cyclosporin A has been shown to reverse drug resistance, but its mechanism of action is unclear. In this study, weekly exposures of A2780DDP cells to cyclosporin A resulted in the evolution of a revertant cell line A2780DDP/CSA that was sensitive to cisplatin again and suppressed the induction of genes necessary for the repair of drug-induced DNA damage.
大多数癌症化疗药物旨在直接或间接损伤DNA。细胞对这些药物产生抗性的一种机制是DNA修复增强。对顺铂耐药的人卵巢癌细胞（A2780DDP）在接受顺铂治疗后，癌基因、DNA修复酶和胸苷合成所需酶的基因表达增加3至6倍。环孢素A已被证明可逆转耐药性，但其作用机制尚不清楚。在本研究中，每周将A2780DDP细胞暴露于环孢素A，导致一种回复细胞系A2780DDP/CSA的产生，该细胞系对顺铂再次敏感，并抑制了药物诱导的DNA损伤修复所需基因的诱导。
