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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:
[Gao, Lvfen; Gao, Xuesong; Zhang, Xian] Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, PR China
[Lin, Shaoqiang] College of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510000, 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
[Ouyang, Yuan; Chen, Ming; Li, Ruobin] Jinan University, Guangzhou, Guangdong 510630, 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
期刊:
Life sciences
年:
2018
入藏号:
PMID:29625193
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.

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