机构：[1]State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China四川大学华西医院[2]Department of Gastroenterology, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital, Chengdu 610041, China四川省人民医院[3]Department of Pharmacy,West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China四川大学华西医院[4]Institute of Clinical Trials, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China四川大学华西医院[5]Department of Urology,West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China四川大学华西医院
Prostate cancer (PCa) is a malignant tumor for which there are no effective treatment strategies. In this study, we developed a targeted strategy for prostate-specific membrane-antigen (PSMA)-positive PCa in vitro based on 2-(3-((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (ACUPA) modified polyethylene glycol (PEG)-Cholesterol micelles containing wogonin (WOG), which was named ACUPA-M-WOG. ACUPA-M-WOG was conventionally prepared using a self-assembling method, which produced stable particle size and zeta potential. Moreover, ACUPA-M-WOG showed good drug encapsulating capacity and drug release profiles. Fluorescence activated cell sorting (FACS) results suggested that ACUPA modified PEG-Cholesterol micelles could effectively enhance the drug uptake on PSMA(+) PCa cells, and the cytotoxicity of ACUPA-M-WOG was stronger than other controls according to in vitro cellular proliferation and apoptosis assays, separately through methyl thiazolyl tetrazolium (MTT) and Annexin V/Propidium Iodide (PI) staining. Finally, the molecular mechanisms of ACUPA-M-WOG's effects on human PSMA(+) PCa were investigated, and were mainly the intrinsic or extrinsic apoptosis signaling pathways. The Western blot results suggested that ACUPA-M-WOG could enhance the WOG-induced apoptosis, which was mainly via the intrinsic signaling pathway rather than the extrinsic signaling pathway. In conclusion, ACUPA-M-WOG was successfully developed for WOG-selective delivery to PSMA(+) PCa cells and had stronger inhibition than free drugs, which might make it an effective strategy for PSMA(+) PCa.
基金：
National Natural Science Foundation of China
(81402500), China Postdoctoral Science Foundation Funded Project (2014M560720), and the Support Foundation
of Science and Technology Department of Sichuan Province (2014FZ0039).
第一作者机构：[1]State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China[4]Institute of Clinical Trials, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China[5]Department of Urology,West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
推荐引用方式(GB/T 7714)：
Zhang Hailong,Liu Xiaogang,Wu Fengbo,et al.A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway[J].INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES.2016,17(5):doi:10.3390/ijms17050676.
APA：
Zhang, Hailong,Liu, Xiaogang,Wu, Fengbo,Qin, Feifei,Feng, Ping...&Yang, Li.(2016).A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,17,(5)
MLA：
Zhang, Hailong,et al."A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 17..5(2016)
