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Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma
  1. Y. Liu*,,
  2. L. Chen,
  3. X. He*,
  4. L. Fan,
  5. G. Yang,
  6. X. Chen,
  7. X. Lin*,
  8. L. Du*,
  9. Z. Li*,
  10. H. Ye,
  11. Y. Mao,
  12. X. Zhao* and
  13. Y. Wei
  1. *Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People' s Republic of China;
  2. Department of Gynecology and Obstetrics, Nuclear Industry 416 Hospital, Chengdu, Sichuan, People' s Republic of China; and
  3. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People' s Republic of China
  1. Address correspondence and reprint requests to: Xia Zhao, MD, Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, People' s Republic of China. Email: xia-zhao{at}126.com

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.

  • chemotherapy
  • cisplatin
  • honokiol
  • liposome
  • ovarian carcinoma

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