Liposomal honokiol, a promising agent for treatment of cisplatin-resistant human ovarian cancer.
OBJECTIVE
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.
Luo
Hong
H
Department of Gynecology and Obstetrics, West China Second Hospital and State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China. luohongcd1969@163.com
Zhong
Qian
Q
Chen
Li-juan
LJ
Qi
Xiao-rong
XR
Fu
A-fu
AF
Yang
Han-shuo
HS
Yang
Fan
F
Lin
Hong-gang
HG
Wei
Yu-quan
YQ
Zhao
Xia
X
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000498:Allyl Compounds; D010636:Phenols
D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D002945:Cisplatin; D017705:Lignans; D008081:Liposomes; C533735:liposomal honokiol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols