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Updated: Jul 11, 2026

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Cell detachment modulates TRAIL resistance in ovarian cancer cells by downregulating the phosphatidylinositol

D Lane1, A Cartier, C Rancourt

  • 1Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Québec, Canada.

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society
|September 18, 2007
PubMed

Insights

Cell detachment enhances TRAIL-induced apoptosis in resistant ovarian cancer by reducing Akt activity. This suggests Akt inhibition can sensitize these cells to TRAIL therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a key apoptosis inducer.
  • Ovarian cancer cells often exhibit intrinsic resistance to TRAIL, limiting its therapeutic efficacy.
  • The molecular mechanisms underlying TRAIL resistance in ovarian cancer are not fully elucidated.

Purpose of the Study:

  • To investigate the role of cell detachment in modulating TRAIL sensitivity in resistant ovarian cancer cells.
  • To identify molecular pathways involved in TRAIL resistance and potential sensitization strategies.

Main Methods:

  • Utilized two TRAIL-resistant ovarian cancer cell lines.
  • Assessed apoptosis induction via TRAIL treatment under detached and attached conditions.
  • Measured caspase activation and Akt phosphorylation.
  • Employed caspase-8 inhibitor (IETD) and phosphatidylinositol 3-kinase inhibitor (LY294002).

Main Results:

  • Cell detachment significantly enhanced TRAIL-induced apoptosis in resistant ovarian cancer cells.
  • Detachment led to increased caspase activation, which was reversible with caspase-8 inhibition.
  • Cell detachment suppressed Akt phosphorylation, indicating decreased Akt activity.
  • Inhibition of phosphatidylinositol 3-kinase (PI3K) with LY294002 also enhanced TRAIL-induced apoptosis, particularly in detached cells.

Conclusions:

  • Cell detachment enhances TRAIL-induced apoptosis in TRAIL-resistant ovarian carcinoma cells by reducing Akt activity.
  • Akt inhibition appears to prime these resistant cells for TRAIL-induced apoptosis, suggesting a potential therapeutic strategy.

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