Comparison of Sonidegib and Vismodegib Efficiency in Drug-Sensitive and Resistant Ovarian Cancer Cell Lines—2D and 3D Model Study
4 affiliations
- 1Institute of Biological Sciences, University of Zielona Góra, 65-417 Zielona Góra, Poland
- 2The Doctoral School of Exact and Technical Sciences, University of Zielona Góra, 65-417 Zielona Góra, Poland
- 3Institute of Health Sciences, Collegium Medicum, University of Zielona Góra, 65-417 Zielona Góra, Poland
- 4Department of Histology and Embryology, Poznan University of Medical Sciences, 61-701 Poznań, Poland
Abstract
Ovarian cancer is a leading cause of mortality among gynecological malignancies. Despite the initial effectiveness of chemotherapy, multidrug resistance (MDR), driven by ABC transporters such as P-glycoprotein, limits treatment success by reducing intracellular paclitaxel (PAC) accumulation. Abnormalities in the Cancer Stem Cells signaling pathway Sonic Hedgehog (Shh) play a role in drug resistance development and ovarian cancer progression. We evaluated two Shh pathway inhibitors, Sonidegib (LDE225) and Vismodegib (VIS), in the W1 drug-sensitive ovarian cancer cell line and PAC-resistant sublines, using the 2D monolayer model, as well as the 3D spheroid model, to better simulate conditions of the tumor microenvironment. qPCR analysis showed similar levels of Shh pathway gene expression in 2D and 3D cell culture conditions. PAC-resistant cell lines were 3- to 6-fold more sensitive to both LDE225 and VIS than the PAC-sensitive cell line. LDE225 showed a 6- to 10-fold lower IC50 than Vismodegib, indicating higher potency. Both agents inhibited proliferation and colony formation in a concentration-dependent manner. Differences in IC50 between 2D and 3D dense spheroids formed by the W1 cell line were small, suggesting that high spheroid density does not reduce the activity of LDE225 and VIS against cancer cells. In conclusion, both inhibitors present pleotropic effects against ovarian cancer cells, especially drug-resistant ones, and can be considered as a new treatment opportunity in this cancer. Nevertheless, further investigation of Hedgehog pathway inhibition in more advanced models is required to assess the potential of clinical application for these compounds.
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BibTeX
@article{stasiak2026comparison,
title = {{Comparison of Sonidegib and Vismodegib Efficiency in Drug-Sensitive and Resistant Ovarian Cancer Cell Lines—2D and 3D Model Study}},
author = {Piotr Stasiak and Justyna Sopel and Artur Płóciennik and Monika Świerczewska and Jan Korbecki and Radosław Januchowski},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219883},
url = {https://www.mdpi.com/1422-0067/27/21/9883},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparison of Sonidegib and Vismodegib Efficiency in Drug-Sensitive and Resistant Ovarian Cancer Cell Lines—2D and 3D Model Study
AU - Piotr Stasiak
AU - Justyna Sopel
AU - Artur Płóciennik
AU - Monika Świerczewska
AU - Jan Korbecki
AU - Radosław Januchowski
PY - 2026
DA - 2026/11/04
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219883
UR - https://www.mdpi.com/1422-0067/27/21/9883
AB - Ovarian cancer is a leading cause of mortality among gynecological malignancies. Despite the initial effectiveness of chemotherapy, multidrug resistance (MDR), driven by ABC transporters such as P-glycoprotein, limits treatment success by reducing intracellular paclitaxel (PAC) accumulation. Abnormalities in the Cancer Stem Cells signaling pathway Sonic Hedgehog (Shh) play a role in drug resistance development and ovarian cancer progression. We evaluated two Shh pathway inhibitors, Sonidegib (LDE225) and Vismodegib (VIS), in the W1 drug-sensitive ovarian cancer cell line and PAC-resistant sublines, using the 2D monolayer model, as well as the 3D spheroid model, to better simulate conditions of the tumor microenvironment. qPCR analysis showed similar levels of Shh pathway gene expression in 2D and 3D cell culture conditions. PAC-resistant cell lines were 3- to 6-fold more sensitive to both LDE225 and VIS than the PAC-sensitive cell line. LDE225 showed a 6- to 10-fold lower IC50 than Vismodegib, indicating higher potency. Both agents inhibited proliferation and colony formation in a concentration-dependent manner. Differences in IC50 between 2D and 3D dense spheroids formed by the W1 cell line were small, suggesting that high spheroid density does not reduce the activity of LDE225 and VIS against cancer cells. In conclusion, both inhibitors present pleotropic effects against ovarian cancer cells, especially drug-resistant ones, and can be considered as a new treatment opportunity in this cancer. Nevertheless, further investigation of Hedgehog pathway inhibition in more advanced models is required to assess the potential of clinical application for these compounds.
SN - 1422-0067
ER -