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YM155 enhances docetaxel efficacy in ovarian cancer

Li-Jiao Hou1, Xiao-Xiu Huang1, Li-Na Xu1

  • 1Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000, Zhejiang, China.

American Journal of Translational Research
|April 12, 2018
PubMed

Insights

YM155, a survivin inhibitor, enhances docetaxel efficacy in ovarian cancer cells by inducing apoptosis. This combination therapy may overcome docetaxel resistance, offering a new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Docetaxel is a key chemotherapy drug for various cancers.
  • Emergence of drug resistance limits docetaxel's long-term efficacy.
  • Survivin is a protein implicated in cancer cell survival and resistance.

Purpose of the Study:

  • To investigate the impact of YM155 on docetaxel efficacy in ovarian cancer.
  • To explore the mechanisms underlying YM155's effects, including survivin suppression and reactive oxygen species (ROS) generation.
  • To assess the potential of combining YM155 and docetaxel for ovarian cancer treatment.

Main Methods:

  • Ovarian cancer cell lines (parental and docetaxel-resistant) were treated with YM155 and/or docetaxel.
  • Cell growth inhibition, cell cycle arrest, and apoptosis were assessed.
  • Survivin expression and intracellular ROS levels were measured.
  • The effects of antioxidants N-acetylcysteine (NAC) and glutathione (GSH) were evaluated.

Main Results:

  • YM155 demonstrated anticancer activity by inhibiting growth, causing cell cycle arrest, and inducing apoptosis through survivin downregulation in ovarian cancer cells.
  • YM155 increased intracellular ROS levels, contributing to apoptosis, particularly in sensitive cells.
  • YM155 potentiated the anti-proliferative and pro-apoptotic effects of docetaxel in ovarian cancer cells.
  • YM155's effects on ROS and apoptosis were partially reversed by antioxidants in sensitive cells but not in resistant cells.

Conclusions:

  • YM155 exhibits anticancer properties and enhances docetaxel efficacy in ovarian cancer.
  • The combination of YM155 and docetaxel presents a promising therapeutic strategy for ovarian cancer, potentially overcoming resistance.
  • Targeting survivin and modulating ROS may be key mechanisms in this combined approach.
Keywords:
Ovarian cancerYM155docetaxel

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