Perez R P, Hamilton T C, Ozols R F
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Pharmacol Ther. 1990;48(1):19-27. doi: 10.1016/0163-7258(90)90015-t.
The curative potential of chemotherapy for ovarian cancer is frequently not realized due to platinum and alkylating agent resistance. Mechanisms which may contribute to the resistant phenotype include alterations in drug transport, increased levels of sulfhydryl molecules (and/or related enzymes), and enhanced DNA repair. We have developed several ovarian cancer cell lines resistant to platinum compounds and alkylating agents. Increased levels of glutathione and enhanced DNA repair are major determinants of chemoresistance in these cells. Modulation of these processes with buthionine sulfoximine (BSO), aphidicolin, arc-C, etc. partially reverses in vitro resistance. Similar clinical treatment strategies are under investigation.
由于铂类和烷化剂耐药性，卵巢癌化疗的治愈潜力常常无法实现。可能导致耐药表型的机制包括药物转运改变、巯基分子（和/或相关酶）水平升高以及DNA修复增强。我们已经建立了几种对铂类化合物和烷化剂耐药的卵巢癌细胞系。谷胱甘肽水平升高和DNA修复增强是这些细胞化疗耐药的主要决定因素。用丁硫氨酸亚砜胺（BSO）、阿非科林、arc-C等调节这些过程可部分逆转体外耐药性。类似的临床治疗策略正在研究中。
