Liposomal honokiol, a promising agent for treatment of cisplatin-resistant human ovarian cancer

Purpose Honokiol has been receiving attention as an anticancer agent because of its anti-tumor effect. In the current study, we encapsulated honokiol with liposome and tested it on cisplatin-sensitive (A2780s) and -resistant (A2780cp) human ovarian cancer models. Methods The anti-tumor activity of liposomal honokiol (Lipo-HNK) was evaluated in nude mice bearing A2780s and A2780cp s.c. tumors. Mice were treated twice weekly with i.v. administration of Lipo-HNK (10 mg/kg), control liposome (10 mg/kg), 0.9% NaCl solution or weekly with intraperitoneally administered cisplatin (5 mg/kg) for 3 weeks. Tumor volume and survival time were observed. Assessment of apoptotic cells by TUNEL assay was conducted in tumor tissue. Microvessel density within tumor tissue was determined by CD34 immunohistochemistry. For in vitro study, induction of apoptosis by Lipo-HNK was examined by PI staining fluorescence microscopy, DNA fragmentation assay and flow cytometric analysis. Results Administration of Lipo-HNK resulted in significant inhibition (84-88% maximum inhibition relative to controls) in the growth of A2780s and A2780cp tumor xenografts and prolonged the survival of the treated mice. These anti-tumor responses were associated with marked increases in tumor apoptosis, and reductions in intratumoral microvessel density. Conclusions The present findings suggest that Lipo-HNK may provide an effective approach to inhibit tumor growth in both cisplatin sensitive and -resistant human ovarian cancer with minimal side effects.