BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells

被引：120

作者：

Yang, CH

Schneider, E

Kuo, ML

Volk, EL

Rocchi, E

Chen, YC

机构：

[1] Natl Taiwan Univ Hosp, Dept Oncol, Taipei 10016, Taiwan

[2] Natl Taiwan Univ, Coll Med, Grad Inst Med, Taipei, Taiwan

[3] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA

[4] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY USA

[5] Natl Taiwan Univ, Coll Med, Inst Toxicol, Taipei, Taiwan

[6] Natl Taiwan Univ Hosp, Dept Lab Med, Taipei, Taiwan

来源：

BIOCHEMICAL PHARMACOLOGY | 2000年 / 60卷 / 06期

关键词：

topotecan; BCRP; mitoxantrone; multidrug resistance;

D O I：

10.1016/S0006-2952(00)00396-8

中图分类号：

R9 [药学];

学科分类号：

1007 ;

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] (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.

引用

页码：831 / 837

页数：7

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