IR@PKUHSC  > 北京大学临床肿瘤学院
学科主题临床医学
Down-regulation of c-fos by shRNA sensitizes adriamycin-resistant MCF-7/ADR cells to chemotherapeutic agents via P-glycoprotein inhibition and apoptosis augmentation
Shi, Ruizan1; Peng, Hongwei2,3,4,5; Yuan, Xiangfei3,4,5; Zhang, Xiuli3,4,5; Zhang, Yanjun3,4,5; Fan, Dongmei3,4,5; Liu, Xuyi6; Xiong, Dongsheng3,4,5
关键词Multidrug Resistance (Mdr) P-glycoprotein (P-gp) Apoptosis Resistance C-fos Molecular Target
刊名JOURNAL OF CELLULAR BIOCHEMISTRY
2013-08-01
DOI10.1002/jcb.24533
114期:8页:1890-1900
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]MULTIDRUG-RESISTANCE ; CDNA MICROARRAY ; BREAST-CANCER ; DOXORUBICIN ; DEATH ; TRANSCRIPTION ; PATHWAYS ; THERAPY ; FAMILY ; TRANSPORTER
英文摘要

Multidrug resistance (MDR) is a major hurdle in the treatment of cancer. Research indicated that the main mechanisms of most cancers included so-called pump (P-glycoprotein, P-gp) and non-pump (apoptosis) resistance. Identification of novel signaling molecules associated with both P-gp and apoptosis will facilitate the development of more effective strategies to overcome MDR in tumor cells. Since the proto-oncogene c-fos has been implicated in cell adaptation to environmental changes, we analyzed its role in mediating pump and non-pump resistance in MCF-7/ADR, an adriamycin (ADR)-selected human breast cancer cell line with the MDR phenotype. Elevated expression of c-fos in MCF-7/ADR cells and induction of c-fos by ADR in the parental drug-sensitive MCF-7 cells suggested a link between c-fos and MDR phenotype. Down-regulation of c-fos expression via shRNA resulted in sensitization of MCF-7/ADR cells to chemotherapeutic agents, including both P-gp and non-P-gp substrates. Further results proved that c-fos down-regulation in MCF-7/ADR cells resulted in decreased P-gp expression and activity, enhanced apoptosis, and altered expression of apoptosis-associated proteins (i.e., Bax, Bcl-2, p53, and PUMA). All above facts indicate that c-fos is involved in both P-gp- and anti-apoptosis-mediated MDR of MCF-7/ADR cells. Based on these results, we propose that c-fos may represent a potential molecular target for resistant cancer therapy, and suppressing c-fos gene expression may therefore be an effective means to temper breast cancer cell′s MDR to cytotoxic chemotherapy. J. Cell. Biochem. 114: 1890-1900, 2013. (c) 2013 Wiley Periodicals, Inc.

语种英语
WOS记录号WOS:000320276000020
项目编号30873091 ; 30971291
资助机构National Natural Science Foundation of China
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50884
专题北京大学临床肿瘤学院
作者单位1.Shanxi Med Univ, Dept Pharmacol, Taiyuan 030001, Shanxi, Peoples R China
2.Nanchang Univ, Dept Pharm, Affiliated Hosp 1, Nanchang 330006, Jiangxi, Peoples R China
3.Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China
4.Chinese Acad Med Sci, Hosp Blood Dis, Tianjin 300020, Peoples R China
5.Peking Union Med Coll, Tianjin 300020, Peoples R China
6.Beijing Univ, Beijing Canc Hosp, Sch Oncol, Beijing 100036, Peoples R China
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Shi, Ruizan,Peng, Hongwei,Yuan, Xiangfei,et al. Down-regulation of c-fos by shRNA sensitizes adriamycin-resistant MCF-7/ADR cells to chemotherapeutic agents via P-glycoprotein inhibition and apoptosis augmentation[J]. JOURNAL OF CELLULAR BIOCHEMISTRY,2013,114(8):1890-1900.
APA Shi, Ruizan.,Peng, Hongwei.,Yuan, Xiangfei.,Zhang, Xiuli.,Zhang, Yanjun.,...&Xiong, Dongsheng.(2013).Down-regulation of c-fos by shRNA sensitizes adriamycin-resistant MCF-7/ADR cells to chemotherapeutic agents via P-glycoprotein inhibition and apoptosis augmentation.JOURNAL OF CELLULAR BIOCHEMISTRY,114(8),1890-1900.
MLA Shi, Ruizan,et al."Down-regulation of c-fos by shRNA sensitizes adriamycin-resistant MCF-7/ADR cells to chemotherapeutic agents via P-glycoprotein inhibition and apoptosis augmentation".JOURNAL OF CELLULAR BIOCHEMISTRY 114.8(2013):1890-1900.
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