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The cdk1-cyclin B complex is involved in everolimus triggered resistance in the PC3 prostate cancer cell line

Igor Tsaur1, Jasmina Makarević, Lukasz Hudak

  • 1Department of Urology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.

Cancer Letters
|September 20, 2011
PubMed

Insights

Prostate cancer cells resistant to everolimus (RAD001) showed increased cell growth due to elevated CDK1-cyclin B complex activity. Targeting this complex may overcome everolimus resistance in prostate cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Prostate cancer remains a significant health concern.
  • Resistance to mTOR inhibitors like everolimus poses a therapeutic challenge.

Purpose of the Study:

  • To investigate the growth potential of prostate cancer cells resistant to everolimus.
  • To elucidate the molecular mechanisms underlying everolimus resistance in PC3 cells.

Main Methods:

  • Comparative analysis of everolimus-sensitive (PC3(par)) and resistant (PC3(res)) prostate cancer cell lines.
  • Flow cytometry to assess cell cycle distribution (G2/M phase).
  • Western blotting to evaluate protein levels (cdk1, cdk2, cyclin B).
  • Gene silencing (siRNA) to investigate the role of cdk1 and cyclin B.

Main Results:

  • PC3(res) cells exhibited similar growth to PC3(par) cells.
  • Low-dose everolimus treatment increased late apoptosis in PC3(par) but decreased it in PC3(res).
  • PC3(res) cells accumulated in the G2/M phase with elevated cdk1, cdk2, and cyclin B.
  • Knockdown of cdk1 or cyclin B significantly inhibited PC3(res) cell growth.

Conclusions:

  • Upregulation of the cdk1-cyclin B complex is a potential mechanism for everolimus resistance in prostate cancer.
  • Enhanced G2/M phase progression driven by cdk1-cyclin B contributes to everolimus resistance.
  • Targeting the cdk1-cyclin B complex may offer a strategy to overcome everolimus resistance in prostate cancer.

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