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学科主题: 临床医学
题名:
A novel indirubin derivative PHII-7 potentiates adriamycin cytotoxicity via inhibiting P-glycoprotein expression in human breast cancer MCF-7/ADR cells
作者: Shi, Ruizan2,3,4; Li, Wei2,3,5; Zhang, Xiuli2,3; Zhang, Yanjun1,2,3; Peng, Hongwei2,3; Xie, Yinliang2,3; Fan, Dongmei2,3; Liu, Rong2,3; Liu, Xuyi6; Xiong, Dongsheng2,3
关键词: PHII-7 ; MDR (multidrug resistance) ; P-gp (P-glycoprotein) ; Reversal effect
刊名: EUROPEAN JOURNAL OF PHARMACOLOGY
发表日期: 2011-11-01
DOI: 10.1016/j.ejphar.2011.07.047
卷: 669, 期:1-3, 页:38-44
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: MEDIATED MULTIDRUG-RESISTANCE ; MULTIPLE-DRUG RESISTANCE ; LEUKEMIA-CELLS ; APOPTOSIS ; MECHANISMS ; STRATEGIES ; CHEMOTHERAPY ; DOXORUBICIN ; CARCINOMA ; REVERSAL
英文摘要:

Multidrug resistance (MDR) is a major impediment to the effective chemotherapy of many human malignancies, and novel MDR reversal agents are desirable for combination therapy to reduce MDR, enhance anti-tumor activity and reduce side effects. Overexpression of P-glycoprotein (P-gp) is the most prevalent cause of MDR in cancer tissues, and resistance to apoptosis is a common characteristic for the multidrug resistant cancer cells. Our group has synthesized a novel potent anti-tumor indirubin derivative, PHII-7. In this study, MCF-7/ADR cells, an adriamycin (ADR)-selected human breast tumor cell line with the MDR phenotype, were used to investigate the anticancer properties of this novel indirubin derivative. Cytotoxicity and apoptosis assays showed that PHII-7 significantly inhibited cell growth, induced apoptosis, potentiated ADR cytotoxicity and restored chemotherapy sensitivity in the MDR cancer cells. Further studies indicated that by down-regulation of P-gp expression, PHII-7 partially inhibited P-gp efflux pump function and increased intracellular accumulation of Rhodamine 123, a P-gp substrate. These results provide a biochemical basis for possible clinical application of PHII-7 alone or in combination with conventional antineoplastic agents in the treatment MDR tumors. (C) 2011 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 30873091 ; 30971291
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000296989500006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54930
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Chinese Acad Med Sci, Dept Pharmacol, State Key Lab Expt Hematol, Inst Hematol, Tianjin 300020, Peoples R China
2.Chinese Acad Med Sci, Hosp Blood Dis, Tianjin 300020, Peoples R China
3.Peking Union Med Coll, Tianjin 300020, Peoples R China
4.Shanxi Med Univ, Dept Pharmacol, Taiyuan 030001, Shanxi, Peoples R China
5.Tianjin Med Univ, Canc Inst & Hosp, Tianjin, Peoples R China
6.Beijing Univ, Sch Oncol, Beijing Canc Hosp, Beijing 100036, Peoples R China

Recommended Citation:
Shi, Ruizan,Li, Wei,Zhang, Xiuli,et al. A novel indirubin derivative PHII-7 potentiates adriamycin cytotoxicity via inhibiting P-glycoprotein expression in human breast cancer MCF-7/ADR cells[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2011,669(1-3):38-44.
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