Dihydroartemisinin selectively inhibits PDGFR alpha-positive ovarian cancer growth and metastasis through inducing degradation of PDGFR alpha protein
文献类型：期刊论文
| 作者 | Li, Xiaoguang2; Ba, Qian2; Li, Jingquan2; Song, Haiyun2; Wang, Hui1,2; Liu, Yanling1; Yue, Qingxi1; Chen, Peizhan1; Zhang, Haibing1; Ying, Hao1 |
| 刊名 | CELL DISCOVERY
 |
| 出版日期 | 2017 |
| 卷号 | 3期号:-页码:UNSP 17042 |
| 关键词 | Dihydroartemisinin Epithelial-mesenchymal transition metastasis ovarian cancer PDGFR alpha |
| ISSN号 | 2056-5968 |
| DOI | 10.1038/celldisc.2017.42 |
| 文献子类 | Article |
| 英文摘要 | To develop traditional medicines as modern pharmacotherapies, understanding their molecular mechanisms of action can be very helpful. We have recently reported that Artemisinin and its derivatives, which are clinically used anti-malarial drugs, have significant effects against ovarian cancer, but the direct molecular targets and related combination therapy have been unclear. Herein, we report that dihydroartemisinin, one of the most active derivatives of Artemisinin, directly targets platelet-derived growth factor receptor-alpha (PDGFR alpha) to inhibit ovarian cancer cell growth and metastasis. Dihydroartemisinin directly binds to the intercellular domain of PDGFRa, reducing its protein stability by accelerating its ubiquitin-mediated degradation, which further inactivates downstream phosphoinositide 3-Kinase and mitogen-activated protein kinase pathways and subsequently represses epithelial-mesenchymal transition, inhibiting cell growth and metastasis of PDGFR alpha-positive ovarian cancer in vitro and in vivo. A combinational treatment reveals that dihydroartemisinin sensitizes ovarian cancer cells to PDGFR inhibitors. Our clinical study also finds that PDGFRa is overexpressed and positively correlated with high grade and metastasis in human ovarian cancer. Considering that Artemisinin compounds are currently clinically used drugs with favorable safety profiles, the results from this study will potentiate their use in combination with clinically used PDGFRa inhibitors, leading to maximal therapeutic efficacy with minimal adverse effects in PDGFR alpha-positive cancer patients. These findings also shed high light on future development of novel Artemisinin-based targeted therapy. |
| 学科主题 | Cell Biology |
| WOS关键词 | EPITHELIAL-MESENCHYMAL TRANSITION ; RECEPTOR TYROSINE KINASES ; CRITICAL ROLES ; ARTEMISININ ; THERAPY ; CELL ; CARCINOMA ; DERIVATIVES ; ARTESUNATE ; TARGET |
| 语种 | 英语 |
| WOS记录号 | WOS:000415998600001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/945]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab food safety Res, Shanghai, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Sch Publ Hlth, Shanghai, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai, Peoples R China; 4.Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77030 USA, |
| 推荐引用方式 GB/T 7714 | Li, Xiaoguang,Ba, Qian,Li, Jingquan,et al. Dihydroartemisinin selectively inhibits PDGFR alpha-positive ovarian cancer growth and metastasis through inducing degradation of PDGFR alpha protein[J]. CELL DISCOVERY,2017,3(-):UNSP 17042. |
| APA | Li, Xiaoguang.,Ba, Qian.,Li, Jingquan.,Song, Haiyun.,Wang, Hui.,...&,.(2017).Dihydroartemisinin selectively inhibits PDGFR alpha-positive ovarian cancer growth and metastasis through inducing degradation of PDGFR alpha protein.CELL DISCOVERY,3(-),UNSP 17042. |
| MLA | Li, Xiaoguang,et al."Dihydroartemisinin selectively inhibits PDGFR alpha-positive ovarian cancer growth and metastasis through inducing degradation of PDGFR alpha protein".CELL DISCOVERY 3.-(2017):UNSP 17042. |
入库方式： OAI收割
来源：上海营养与健康研究所
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