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Updated: Jul 16, 2026
Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
Vismodegib Exerts a Pleotropic Effect on Topotecan-Resistant and Sensitive Ovarian Cancer Cell Lines in 2D and 3D
Piotr Stasiak1,2,3, Justyna Sopel3, Artur Płóciennik3
1Institute of Biological Sciences, University of Zielona Gora, 65-417 Zielona Gora, Poland.
Abstract:
Ovarian cancer remains a leading cause of gynecological cancer-related mortality. Although the standard therapy is usually effective at first, the development of multidrug resistance (MDR) significantly limits the efficacy of the treatment. Topotecan (TOP) is a drug commonly used in second-line therapy. However, the cancer cells eventually become immune to its cytotoxic effect, as they start to produce ATP-binding cassette (ABC) transporters, proteins facilitating drug removal. Breast cancer resistance protein (BCRP) is one such protein, and TOP is its known substrate. Vismodegib, a Sonic Hedgehog pathway (Shh) inhibitor, has demonstrated potential anticancer activity in various malignancies. This study aims to evaluate the effects of Vismodegib treatment on both topotecan-sensitive and -resistant ovarian cancer cell lines, cultured in two-dimensional (2D) and three-dimensional (3D) conditions, as well as the potential of Vismodegib treatment to reverse the acquired drug resistance. Our results suggest that Vismodegib re-sensitizes TOP-resistant cells in both 2D and 3D models. However, further research is needed to evaluate its usefulness in ovarian cancer treatment.
Insights
Vismodegib may help overcome topotecan resistance in ovarian cancer. This study shows Vismodegib re-sensitizes topotecan-resistant cells in 2D and 3D models, suggesting potential for overcoming multidrug resistance.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Ovarian cancer is a major cause of gynecological cancer mortality.
- Multidrug resistance (MDR) limits standard therapy efficacy, often due to ATP-binding cassette (ABC) transporters like Breast Cancer Resistance Protein (BCRP).
- Topotecan (TOP) is a substrate for BCRP and commonly used in second-line therapy.
Purpose of the Study:
- To evaluate Vismodegib's effects on topotecan-sensitive and -resistant ovarian cancer cells.
- To assess Vismodegib's potential to reverse acquired drug resistance.
- To investigate these effects in both 2D and 3D cell culture models.
Main Methods:
- Utilized topotecan-sensitive and -resistant ovarian cancer cell lines.
- Cultured cells in both two-dimensional (2D) and three-dimensional (3D) models.
- Administered Vismodegib treatment to assess its impact on drug sensitivity and resistance.
Main Results:
- Vismodegib demonstrated the ability to re-sensitize topotecan-resistant ovarian cancer cells.
- This effect was observed in both 2D and 3D cell culture models.
- Suggests Vismodegib may overcome acquired resistance mechanisms.
Conclusions:
- Vismodegib shows promise in re-sensitizing topotecan-resistant ovarian cancer cells.
- The findings support further investigation into Vismodegib for ovarian cancer treatment, particularly for overcoming MDR.
- Further research is warranted to confirm its clinical utility.
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