Combination of Tetrandrine With Cisplatin Enhances Cytotoxicity Through Growth Suppression and Apoptosis in Ovarian Cancer in Vitro and in Vivo

Cancer Lett. 2011 May 1;304(1):21-32. doi: 10.1016/j.canlet.2011.01.022. Epub 2011 Feb 17.

Abstract

Cisplatin, as a first-line drug in the chemotherapy of ovarian cancer, poses significant problems in its toxicity to normal tissue and drug resistance. Here, we report that Tetrandrine, with potent anti-cancer effect, significantly enhances the cytotoxicity of cisplatin in ovarian cancer. The in vitro assay indicates that Tetrandrine can markedly increase growth suppression and apoptosis induced by cisplatin and cause redistribution of the cell cycle. Further assay indicates that modulation of Wnt/cadherin signaling pathway contributes to the chemosensitizing effect of Tetrandrine on the cytotoxicity of cisplatin in ovarian cancer. In vivo, the combination of Tetrandrine and cisplatin exhibits the strongest anti-cancer effect compared with each drug alone, with no obvious additional toxicity. These results provide rational evidence supporting the application of Tetrandrine as an adjunct to cisplatin in improvement of chemotherapy in ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Benzylisoquinolines / administration & dosage
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects*
  • Cisplatin / administration & dosage
  • Drug Synergism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • In Vitro Techniques
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Benzylisoquinolines
  • tetrandrine
  • Cisplatin