Vismodegib Exerts a Pleotropic Effect on Topotecan-Resistant and Sensitive Ovarian Cancer Cell Lines in 2D and 3D Cell Culture Models.

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.