Comparison of two-dimensional and three-dimensional culture systems and their responses to chemotherapy in cells representing disease progression of high-grade serous ovarian cancer

Naya El Mokbel ¹, Alicia A Goyeneche ¹, Rewati Prakash ¹

⁰McGill University, Experimental Pathology Unit, Department of Pathology, Faculty of Medicine and Health Sciences, Montreal, QC, Canada.

Biochemistry and Biophysics Reports +

|

October 29, 2024

View abstract on PubMed

Summary

Three-dimensional (3D) cell culture better models ovarian cancer response to chemotherapy than 2D cultures. This advanced preclinical model shows reduced drug sensitivity, reflecting in vivo tumor behavior for improved therapeutic evaluation.

Area Of Science

Oncology
Cell Biology
Pharmacology

Background

High-grade serous ovarian cancer (HGSOC) is frequently diagnosed late, with high mortality due to recurrence and platinum resistance.
Effective preclinical models are crucial for evaluating new therapeutic strategies against HGSOC.
Standard two-dimensional (2D) cell cultures may not fully recapitulate the complex tumor microenvironment.

Purpose Of The Study

To compare two-dimensional (2D) versus three-dimensional (3D) cell culture models for evaluating drug response in ovarian cancer.
To assess the efficacy of carboplatin, paclitaxel, and niraparib in PEO1, PEO4, and PEO6 HGSOC cell lines using both culture methods.
To determine which culture model better reflects in vivo tumor behavior and therapeutic response.

Main Methods

Utilized PEO1, PEO4, and PEO6 high-grade serous ovarian cancer cell lines, derived from a single patient across disease progression.
Cultured cells in both 2D (adherent layers) and 3D (spheroidal structures) formats.
Morphologically characterized cell growth, assessed apoptosis, measured ATP production, and evaluated drug sensitivity to carboplatin, paclitaxel, and niraparib.

Main Results

3D cultures exhibited spheroidal structures with distinct compaction, unlike the flat layers in 2D.
Apoptosis was minimal in 2D but prominent in the inner core of 3D structures, surrounded by proliferating outer cells.
Differential ATP production was observed in 3D, but not 2D, cultures. Drug sensitivity trends were similar, but 3D models showed lower sensitivity compared to 2D.

Conclusions

Three-dimensional (3D) cell culture models demonstrate morphological and physiological differences compared to 2D cultures, including distinct cell death patterns and metabolic activity.
3D models show reduced sensitivity to carboplatin, paclitaxel, and niraparib, suggesting they are more representative of in vivo drug response.
The complexity of 3D cultures makes them a more suitable and potentially predictive preclinical model for evaluating ovarian cancer therapeutics compared to traditional 2D methods.

Keywords:

2D culture 3D culture Anchorage-free Anticancer drugs High grade serous ovarian cancer Multicellular tumor spheroids Ultra-low attachment