Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma.

Abstract

Honokiol, a well-tolerated natural product, can inhibit the proliferation of cancer cells. But its water insolubility hampers its systemic administration for therapy of cancer. As a drug delivery system, the pegylated liposome (PEGL) can increase the water solubility and targeting of the drug. Honokiol has been successfully encapsulated by PEGL in our laboratory. We wondered whether the combination treatment with pegylated liposomal honokiol (H-PEGL) and cisplatin (DDP) could improve the antitumor efficacy in ovarian carcinoma. H-PEGL could introduce apoptosis of SKOV3 cells in vitro, which was quantified by flow cytometric analysis, and the cellular morphologic changes were determined by propidium iodide staining. In a human ovarian carcinoma mouse model, combination treatment with H-PEGL (0.4 mg/day for 30 days; intraperitoneal) and DDP (5 mg/kg on days 7, 11, 15, 19; intraperitoneal) acted synergistically to inhibit tumor growth by 91.48% without notable toxicity, but H-PEGL and DDP alone only inhibit tumor growth by 66.83% and 52.5% as compared to the NaCl solution control, respectively. Assessment of microvessel density and apoptosis index by CD31 and terminal deoxynucleotidyl transferase-mediated nick end labeling immunohistochemistry respectively suggested that the antitumor activity of H-PEGL is mediated by angiogenesis inhibition and introduction of apoptosis. Our results showed us a splendid prospect of the clinical application of combination treatment on patients suffering from ovarian cancer with H-PEGL and DDP.

• Authors: Y Liu, L Chen, X He, L Fan, G Yang, X Chen, X Lin, L DU, Z Li, H Ye, Y Mao, X Zhao, Y Wei
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) 2008 Jul-Aug Vol. 18 Issue 4 Pg. 652-9 ISSN: 1525-1438 [Electronic] England
• PMID: 17892458 (Publication Type: Journal Article)

Chemical References

• Biphenyl Compounds
• Lignans
• Liposomes
• honokiol
• Polyethylene Glycols
• Cisplatin

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Apoptosis (drug effects)
• Biphenyl Compounds (administration & dosage, pharmacology)
• Carcinoma (blood supply, drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cisplatin (administration & dosage, pharmacology)
• Drug Synergism
• Female
• Humans
• Lignans (administration & dosage, pharmacology)
• Liposomes (administration & dosage)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neovascularization, Pathologic (drug therapy)
• Ovarian Neoplasms (blood supply, drug therapy, pathology)
• Polyethylene Glycols (administration & dosage)
• Treatment Outcome
• Xenograft Model Antitumor Assays