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Icaritin induces ovarian cancer cell apoptosis through activation of p53 and inhibition of Akt/mTOR pathway

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成果类型:
期刊论文
作者:
Gao, Lvfen;Chen, Ming;Ouyang, Yuan;Li, Ruobin;Zhang, Xian;Gao, Xuesong;Wang, Xiaoyu*;Lin, Shaoqiang
通讯作者:
Wang, Xiaoyu
作者机构:
[Li, Ruobin; Chen, Ming; Ouyang, Yuan] Jinan University, Guangzhou, Guangdong 510630, PR China
[Zhang, Xian; Gao, Xuesong; Gao, Lvfen] Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, PR China
[Wang, Xiaoyu] Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, PR China. Electronic address: xywang62@163.com
[Lin, Shaoqiang] College of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510000, PR China
通讯机构:
[Wang, Xiaoyu] Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, PR China. Electronic address:
语种:
英文
关键词:
OC;ovarian cancer;PARP;poly-ADP-ribose polymerase;PDXs;patient-derived xenografts;CDDP;cis-platinum;Akt;protein kinase B;mTOR;mammalian target of rapamycin;MTS;3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt;Ovarian cancer;Apoptosis;p53;Akt;mTOR;Icaritin
期刊:
Life Sciences
ISSN:
0024-3205
年:
2018
卷:
202
页码:
188-194
文献类别:
WOS:Article
所属学科:
ESI学科类别:生物学与生物化学;WOS学科类别:Medicine, Research & Experimental;Pharmacology & Pharmacy
入藏号:
WOS:000433559000024;PMID:29625193
基金类别:
Medical Scientific Research Foundation of Guangdong Province [A2017203]; Project of Traditional Chinese Medicine in Guangdong [20162045]
机构署名:
本校为其他机构
院系归属:
临床医学院
摘要:
AIMS: Ovarian cancer (OC) has the highest mortality rate of all gynecological cancers. Currently, the first-line OC treatment consists of cytoreductive surgery and platinum-based chemotherapy. However, most patients develop chemoresistance after the first-line treatment limits the success of treatment. Therefore, there is an urgent need to identify effective therapeutic agents. MAIN METHODS: Cell viabilities were detected by MTS assay; Annexin V-FITC/PI assay and western blotting assay were performed to analyze the apoptotic cells in vitro; An immunofluorescence assay was performed to analyze the TUNEL(+) apoptotic cells in vivo; Patient-derived xenografts were established to test the in vivo antitumor effects; The key proteins of p53, caspase-mediated apoptotic pathway and Akt/mTOR pathway were detected by Western blotting. KEY FINDINGS: Icaritin, a prenylflavonoid derivative from Epimedium Genus, inhibited the proliferation of drug-sensitive OC cells (OV2008 and C13*) and cisplatin resistant OC cells A2780cp. Icaritin induced OC cell apoptosis in vitro, as indicated by the increase of Annexin V(+)/PI(+) apoptotic cells analyzed with flow cytometry, and the cleavage of caspase 9, caspase 3 and poly-ADP-ribose polymerase (PARP) detected with western blotting. Icaritin also inhibited tumor growth and induced OC cells apoptosis in patient-derived xenografts, as indicated by the tumor growth delay and increase of TUNEL-positive cells in tumor tissues. The icaritin-induced OC cell apoptosis may be associated with the activation of p53 and the suppression of Akt/mTOR pathway. SIGNIFICANCE: This study sheds light on the underlying mechanisms of antitumor effect of icaritin, and warrants clinical trial for treatment of OC.
参考文献:
Brady CA, 2010, J CELL SCI, V123, P2527, DOI 10.1242/jcs.064501
Feng XX, 2013, INT REV CEL MOL BIO, V304, P227, DOI 10.1016/B978-0-12-407696-9.00005-1
Follo Matilde Y, 2015, Adv Biol Regul, V57, P10, DOI 10.1016/j.jbior.2014.10.004
Grinkevich VV, 2017, CANCER CELL, V31, P724, DOI 10.1016/j.ccell.2017.04.014
Guo YM, 2011, EUR J PHARMACOL, V658, P114, DOI 10.1016/j.ejphar.2011.02.005

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