Investigations on the mechanisms of methotrexate resistance in a cisplatin-resistant L1210 murine leukemia cell subline
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- 作者：Diana H. Wroblewski ; Alok Bhushan ; Yongzhi Xuan ; Bradford T. Brinton ; Thomas R. Tritton and Miles P. Hacker
- 关键词：Key words ; Methotrexate ; Cisplatin ; Drug resistance
- 刊名：Cancer Chemotherapy and Pharmacology
- 出版年：1996
- 出版时间：January 1996
- 年：1996
- 卷：37
- 期：4
- 页码：337-342
- 全文大小：354 KB
文摘
We report a murine leukemia cell variant (L1210/DDP), selected for cisplatin (DDP) resistance, to be cross-resistant to methotrexate (MTX). Cross-resistance of L1210 cells to DDP and MTX has been observed by others, and has also been recorded in P388 murine leukemia and SSC-25 human squamous carcinoma cells. We demonstrated that MTX resistance is not due to dihydrofolate reductase (DHFR) gene amplification, increased DHFR enzyme activity or decreased MTX binding to the target enzyme. Of the mechanisms commonly proposed for MTX resistance, only differences in transport were observed when comparing sensitive (L1210/0) and resistant (L1210/DDP) cells. Our results suggest that MTX resistance in L1210/DDP cells is due to altered methotrexate uptake.