PhD Scientific Days 2021

PH_I_P: Pharmaceutical Sciences I. Posters

Synergy of Bortezomib and TIC10 in melanoma in vitro

Angela Takacs
Department of Genetics, Cell and Immunobiology, Budapest

Text of the abstract

Combination antitumor treatments are essential parts of modern tumor therapy as – compared to monotherapies – (i) they are more effective; (ii) the dose of the compounds can be reduced; (iii) therefore the side effects are improved. Our research group previously demonstrated the antitumor character of bortezomib (BOZ) in A2058 melanoma cells. Unfortunately, dose-related side effects are common during BOZ therapy, which could be prevented by reducing the dose of BOZ. This study aims to characterize synergistic combinations of BOZ with TRAIL-inducing compound (TIC10), where the doses can be cut down but the efficacy is preserved. Endpoint cell viability assays were performed on A2058 cells and synergism of BOZ and TIC10 was observed after 72h. Synergism was further validated in real-time impedimetric assay and our results showed, that BOZ treated melanoma cells survived the treatment, which effect was not registered in the co-treatments. Treatment with the combinations resulted in increased apoptosis, which was not accompanied by enhanced cytotoxicity observed in an LDH assay. Nevertheless, the expression of death receptor 5 (DR5) was increased on the cell surface without transcriptional regulation. In summary, our findings support the theory that the application of BOZ and TIC10 in combination could provide higher efficacy in vitro.
This research was funded by National Competitiveness and Excellence Programme
(NVKP_16-1-2016-0036), by the ÚNKP-19-3-I-SE-49 New National Excellence Program of the
Ministry for Innovation and Technology and by the EFOP-3.6.3-VEKOP-16-2017-00009 program.

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences