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学科主题: 药学
题名:
Dopamine enhances the response of sunitinib in the treatment of drug-resistant breast cancer: Involvement of eradicating cancer stem-like cells
作者: Wang, Siyuan2; Mou, Zhenzhen2; Ma, Yuanheng2; Li, Jian2; Li, Jingyun2; Ji, Xiwei2; Wu, Kehua2; Li, Liang1,2; Lu, Wei1,2; Zhou, Tianyan1,2
关键词: Cancer stem-like cells ; Dopamine ; Dopamine receptor ; Sunitinib ; Combination therapy ; Drug-resistance
刊名: BIOCHEMICAL PHARMACOLOGY
发表日期: 2015-05-15
DOI: 10.1016/j.bcp.2015.03.013
卷: 95, 期:2, 页:98-109
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]: THERAPEUTIC TARGET ; OVARIAN-CARCINOMA ; IDENTIFICATION ; RECEPTOR ; GROWTH ; TUMORS ; ANGIOGENESIS ; INHIBITION ; ACTIVATION ; EXPRESSION
英文摘要:

Growing evidence suggests that the efficacy of sunitinib in breast cancer may be limited by increasing the population of cancer stem-like cells (CSCs). Hence the concurrent use of CSCs-targeting agents is required. Previous results indicated that dopamine receptor (DR) may serve as a potential therapeutic target of anti-CSCs therapies. This study focused on evaluating the effect of dopamine (an agonist of DR) on the enhancement of sunitinib′s efficacy in the treatment of drug-resistant breast cancer, investigating the involved activation type of DR pathway and exploring the underlying anti-CSCs mechanisms. MCF-7 cells, MCF-7/Adr cells and breast cancer stem-like cells (BCSCs) were used for in vitro study. Moreover, MCF-7/Adr cells and BCSCs were selected as drug-resistant cell lines and further used for in vivo development of the xenograft animal models. Our results showed that dopamine greatly synergized the inhibitory effect of sunitinib in the drug-resistant cells and strikingly enhanced the response of sunitinib in both xenograft models. It was found that dopamine significantly down-regulated the expression of BCSCs markers (CD44*/CD24(-)) in vitro and in vivo. In addition, dopamine remarkably induced the apoptosis of BCSCs, markedly inhibited the Wnt signaling pathway and activated the apoptotic associated signals. The activation of dopamine receptor D1 (D1DR) pathway may be involved in the underlying mechanism as D1DR′s antagonist SCH23390 completely reversed the combined effects. In conclusion, dopamine may eradicate CSCs and it significantly enhances the response of sunitinib in the treatment of drug-resistant breast cancer. (C) 2015 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 81473277
项目资助者: National Natural Science Foundation of China (NSFC) ; Pfizer
WOS记录号: WOS:000354007900002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66480
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: 1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Siyuan,Mou, Zhenzhen,Ma, Yuanheng,et al. Dopamine enhances the response of sunitinib in the treatment of drug-resistant breast cancer: Involvement of eradicating cancer stem-like cells[J]. BIOCHEMICAL PHARMACOLOGY,2015,95(2):98-109.
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