Icariin and icaritin stimulate the proliferation of SKBr3 cells through the GPER1-mediated modulation of the EGFR-MAPK signaling pathway
Ma, Hai-Rong; Wang, Jie; Chen, Yiu-Fai; Chen, Hua; Wang, Wei-Shan; Aisa, Haji Akber; Aisa, HA
2014
发表期刊INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
ISSN1107-3756
卷号33期号:6页码:1627-1634
摘要

Icariin (ICA) and icaritin (ICT), with a similar structure to genistein, are the important bioactive components of the genus Epimedium, and regulate many cellular processes. In the present study, using the estrogen receptor (ER)-negative breast cancer cell line, SKBr3, as a model, we examined the hypothesis that ICA and ICT at low concentrations stimulate SKBr3 cell proliferation in vitro through the functional membrane, G protein-coupled estrogen receptor 1 (GPER1), mediated by the epithelial growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) signaling pathway. MTT assay revealed that ICA and ICT at doses of 1 nM to 1 mu M markedly stimulated SKBr3 cell proliferation in a dose-dependent manner. The ICA- and ICT-stimulated cell growth was completely suppressed by the GPER1 antagonist, G-15, indicating that the ICA- and ICT-stimulated cell proliferation was mediated by GPER1 activation. Semi-quantitative RT-PCR analysis revealed that treatment with ICA and ICT enhanced the,transcription of c-fos, a proliferation-related early gene. The ICA- and ICT-stimulated mRNA expression was markedly attenuated by G-15, AG-1478 (an EGFR antagonist) or PD98059 (a MAPK inhibitor). Our data also demonstrated that ICA and ICT increased the phosphorylation of ERK1/2. The ICA- and ICT-stimulated ERK1/2 phosphorylation was blocked by pre-treatment of the cells with G-15 and AG-1478 or PD 98059. Flow cytometric analysis confirmed that the ICA- and ICT-stimulated SKBr3 cell proliferation involved the GPER1-mediated modulation of the EGFR-MAPK signaling pathway. To the best of our knowledge, our current findings demonstrate for the first time that ICA and ICT promote the progression of ER-negative breast cancer through the activation of membrane GPER1.

关键词Icariin Icaritin g Protein-coupled Estrogen Receptor 1 Cell Proliferation Epithelial Growth Factor Receptor-mitogen-activated Protein Kinase Pathway
DOI10.3892/ijmm.2014.1722
收录类别SCI
WOS记录号WOS:000336554900031
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.xjipc.cas.cn/handle/365002/3780
专题省部共建新疆特有药用资源利用重点实验室
通讯作者Aisa, HA
作者单位Chinese Acad Sci, Key Lab Plant Resources & Chem Arid Zone, Urumqi 830011, Xinjiang, Peoples R China;Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, State Key Lab Basis Xinjiang Indigenous Med Plant, Urumqi 830011, Xinjiang, Peoples R China;Shihezi Univ, Coll Pharm, Key Lab Xinjiang Endem Phytomed Resources, Minist Educ, Shihezi 832002, Peoples R China;Univ Alabama Birmingham, Dept Med, Vasc Biol & Hypertens Program, Birmingham, AL 35294 USA;Shihezi Univ, Sch Med, Shihezi 832002, Peoples R China
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Ma, Hai-Rong,Wang, Jie,Chen, Yiu-Fai,et al. Icariin and icaritin stimulate the proliferation of SKBr3 cells through the GPER1-mediated modulation of the EGFR-MAPK signaling pathway[J]. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,2014,33(6):1627-1634.
APA Ma, Hai-Rong.,Wang, Jie.,Chen, Yiu-Fai.,Chen, Hua.,Wang, Wei-Shan.,...&Aisa, HA.(2014).Icariin and icaritin stimulate the proliferation of SKBr3 cells through the GPER1-mediated modulation of the EGFR-MAPK signaling pathway.INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,33(6),1627-1634.
MLA Ma, Hai-Rong,et al."Icariin and icaritin stimulate the proliferation of SKBr3 cells through the GPER1-mediated modulation of the EGFR-MAPK signaling pathway".INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 33.6(2014):1627-1634.
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