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Updated: Oct 6, 2025

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
07:59

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1

Published on: December 5, 2020

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The Anti-Proliferative Effect of PI3K/mTOR and ERK Inhibition in Monolayer and Three-Dimensional Ovarian Cancer Cell

Elizabeth Dunn1, Kenny Chitcholtan2, Peter Sykes2

  • 1School of Biological Sciences, University of Canterbury, Christchurch 8041, New Zealand.

Cancers
|January 21, 2022
PubMed

Insights

Combining PI3K/mTOR and ERK inhibitors shows synergistic effects against ovarian cancer cells, offering a potential strategy to overcome treatment resistance. Three-dimensional models revealed varying sensitivities, highlighting the need for further preclinical research.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Ovarian cancer is often diagnosed at advanced stages, leading to resistance to chemotherapy.
  • The PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways are frequently mutated in ovarian cancer, making them therapeutic targets.
  • Monotherapies targeting these pathways have shown limited efficacy, possibly due to alternative pathway activation.

Purpose of the Study:

  • To investigate the efficacy of combined PI3K/mTOR and ERK inhibition in ovarian cancer.
  • To evaluate the impact of 2D (monolayer) versus 3D (cell aggregate) models on drug sensitivity.

Main Methods:

  • Four human ovarian cancer cell lines were treated with combined PI3K/mTOR (BEZ235) and ERK (SCH772984) inhibitors.
  • Cells were cultured as both monolayers and three-dimensional aggregates (spheroids).
  • Cellular proliferation and synergistic effects were assessed.

Main Results:

  • The inhibitor combination demonstrated synergistic antiproliferative effects in most monolayer and 3D cultures.
  • Sensitivity to inhibitors was generally reduced in 3D aggregates compared to monolayers.
  • OV-90 spheroids showed sensitivity, while OVCAR8 spheroids exhibited resistance to the combination therapy.

Conclusions:

  • Combined PI3K/mTOR and ERK inhibition is a promising strategy for overcoming ovarian cancer treatment resistance.
  • The choice of 3D model can significantly influence drug sensitivity, necessitating careful consideration in preclinical studies.
  • Further preclinical investigation is warranted to explore this combination therapy for ovarian cancer.
Keywords:
BEZ235SCH772984combination chemotherapydactolisibovarian cancerspheroidsthree-dimensional model

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