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.