title: Induction of apoptosis and inhibition of angiogenesis by PEGylated liposomal quercetin in both cisplatin-sensitive and cisplatin-resistant ovarian cancers.
abstract: The clinical efficiency of cisplatin against ovarian cancer is often limited by the development of drug resistance. In this work, we investigated PEGylated liposomal quercetin (Lipo-Que) on cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) human ovarian cancer models in vitro and in vivo to reveal whether a cisplatin-resistant ovarian cancer has susceptibility to quercetin (Que) and the mechanism of its antitumor activity. Lipo-Que was prepared using a solid dispersion method, and the obtained Lipo-Que is monodisperse with a mean diameter of 163 +/-10 nm. Besides, in vitro drug release assay showed a sustained release behavior of Lipo-Que. In vitro experiments suggested that Lipo-Que inhibited cell proliferation, induced apoptosis, and induced cell cycle arrest in both A2780s and A2780cp cells. Furthermore, antitumor activity of Lipo-Que was investigated in both cisplatin-sensitive and cisplatin-resistant human ovarian tumor xenograft models in nude mice. Lipo-Que significantly suppressed tumor growth in both models in comparison with free Que, blank liposomes (Lipo), or normal saline (NS). Furthermore, immunohistochemistry and immunofluorescence tests revealed that Lipo-Que induced apoptosis, decreased microvessel density, and inhibited proliferation of tumors in both A2780s and A2780cp tumor models. Therefore, our results suggest that Lipo-Que is an effective agent to inhibit tumor growth in both cisplatin-sensitive and cisplatin-resistant human ovarian cancers.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, and Department of Gynecology and Obstetrics, Second West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Qida
authors.initials: Q
authors.lastname: Long
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiel
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Huang
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Wu
authors.forename: Hecheng
authors.initials: H
authors.lastname: Zhang
authors.forename: Shaoquan
authors.initials: S
authors.lastname: Xiong
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Liu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Changyang
authors.initials: C
authors.lastname: Gong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D009389:Neovascularization, Pathologic / Q000150:complications / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011794:Quercetin / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D008081:Liposomes; D053769:Nanocapsules; D011092:Polyethylene Glycols; D011794:Quercetin; D002945:Cisplatin