https://scholars.lib.ntu.edu.tw/handle/123456789/562945
標題: | BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells | 作者: | CHIH-HSIN YANG Schneider E. Kuo M.-L. Volk E.L. Rocchi E. YAO-CHANG CHEN |
公開日期: | 2000 | 卷: | 60 | 期: | 6 | 起(迄)頁: | 831-837 | 來源出版物: | Biochemical Pharmacology | 摘要: | We have previously described a mitoxantrone-resistant MCF7 cell line that is cross-resistant to topotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin (CPT-11), and 9-aminocamptothecin, but not to camptothecin. A novel mechanism that resulted in decreased topotecan accumulation in MCF7/MX cells was proposed (Yang et al. Cancer Res 55: 4004-4009, 1995). We now have developed a topotecan-resistant cancer cell line from wild-type MCF7 cells. MCF7/TPT300 cells were 68.9-fold resistant to topotecan, 68.3-fold to 10-hydroxy-7-ethylcamptothecin (SN-38), and 116-fold to mitoxantrone, but only 4.1-fold to camptothecin. Topotecan efflux was increased in MCF7/TPT300 cells compared with MCF7/WT cells, and this increase was reversed upon ATP depletion by sodium azide, suggesting an energy-dependent drug efflux mechanism. However, MCF7/TPT300 cells did not overexpress P-glycoprotein or the multidrug resistance-associated protein (MRP1). In contrast, overexpression of the breast cancer resistance protein (BCRP/MXR/ABCP) was observed in MCF7/TPT300 cells as well as DNA topoisomerase I down-regulation. Our data suggest that enhanced topotecan efflux contributes partly to topotecan resistance in MCF7/TPT300 cells, possibly mediated by BCRP/MXR/ABCP. (C) 2000 Elsevier Science Inc. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/562945 | ISSN: | 0006-2952 | DOI: | 10.1016/S0006-2952(00)00396-8 | SDG/關鍵字: | 7 ethyl 10 hydroxycamptothecin; 9 aminocamptothecin; breast cancer resistance protein; camptothecin; DNA topoisomerase; doxorubicin; etoposide; fluorouracil; glycoprotein P; irinotecan; mitoxantrone; multidrug resistance protein; paclitaxel; topotecan; unclassified drug; article; breast carcinoma; cancer cell culture; cancer resistance; controlled study; cytotoxicity; drug transport; human; human cell; multidrug resistance; priority journal; protein expression; Adenosine Triphosphate; Antineoplastic Agents; ATP-Binding Cassette Transporters; Biological Transport; Breast Neoplasms; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; DNA-Binding Proteins; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Gene Expression Regulation, Neoplastic; Humans; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; P-Glycoprotein; Topotecan; Tumor Cells, Cultured |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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