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YM155 Reverses Statin Resistance in Renal Cancer by Reducing Expression of Survivin

Takashi Nitta1, Hidekazu Koike2, Takeshi Miyao1

  • 1Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Anticancer Research
|December 25, 2016
PubMed
Abstract

Insights

YM155, a survivin inhibitor, reverses statin resistance in renal cell cancer (RCC). This drug overcomes resistance and enhances chemotherapy efficacy in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Renal cell carcinoma (RCC) often exhibits resistance to statin therapy.
  • Survivin is a protein overexpressed in various cancers, including RCC.
  • Statin resistance in RCC poses a significant clinical challenge.

Purpose of the Study:

  • To investigate if YM155, a survivin inhibitor, can reverse statin resistance in RCC.
  • To evaluate the efficacy of YM155 alone and in combination with simvastatin in preclinical RCC models.

Main Methods:

  • Induced simvastatin resistance in a human RCC cell line (Caki-1-staR).
  • Utilized in vitro cell culture and in vivo mouse xenograft models.
  • Assessed survivin gene expression, cell proliferation, and tumor growth.

Main Results:

  • Survivin expression was higher in statin-resistant RCC cells.
  • YM155 dose-dependently reduced survivin expression and cell proliferation.
  • YM155 reversed simvastatin resistance in vitro and inhibited tumor growth in vivo.
  • YM155 enhanced the antitumor effects of simvastatin.

Conclusions:

  • Inhibition of survivin by YM155 is a viable strategy to overcome statin resistance in RCC.
  • YM155 demonstrates potential as a therapeutic agent for statin-resistant RCC.
Keywords:
Kidney neoplasmscombinationdrug therapyinhibitor of apoptosis proteinsstatin

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