Sağlık Bilimleri Yüksek Lisans Tezleri / Master Degree

Permanent URI for this collectionhttps://hdl.handle.net/11452/24

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    Investigation of the effects of supplementary therapy candidate molecules in breaking chemotherapy resistance in glioblastoma cells and retrospectively supporting the findings with primary tumors
    (Bursa Uludağ Üniversitesi, 2023-08-11) Ferah, Sena; Tunca, Berrin; Sağlık Bilimleri Enstitüsü; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0001-9076-1855
    In the current study, it was aimed to examine the effects of fisetin and berberine, which are predicted to have prospects of complementary therapy, on the potential to elucidate drug resistance and increase the success of temozolomide (TMZ) in the treatment of non-resistant, natural, and acquired resistant glioblastoma (GBM) cells in combination with TMZ in both normoxic and hypoxic environment conditions that are more compatible with the cancer microenvironment, and to validate the findings in the study in primary brain tumor cells. For this purpose, initially, the therapeutic efficacy of fisetin and berberine, alone or in combination with TMZ, on cell proliferation was determined by the xCELLigence method, their effectiveness on cell cycle and apoptosis by flow cytometric method, their effectiveness on cell aggressiveness was determined by wound healing under normoxic conditions, colony test and 3D culture model, and wound healing test in hypoxic conditions. Furthermore, the efficacy of fisetin, which was determined to be more effective at a lower dose for GBM treatment, in combination with TMZ, the MSH2 and ZEB1 gene expression levels between TMZ-resistant and sensitive cell lines were investigated and validated in primary brain tumors with different characteristics. Hence, the findings of the current study showed that fisetin had anti-tumor activity in both normoxic and hypoxic environments by functional analysis and showed that it increased the activity of TMZ in resistant cells, especially in combination with TMZ. Consonantly, TMZ+Fisetin treatment was found to be effective in increasing MSH2 levels and decreasing ZEB1 levels in both cell lines and GBM primary patients. Consequently, current findings supporting the efficacy of TMZ+Fisetin combination therapy indicate that fisetin, which can be effective in breaking resistance even in different mechanisms, may have the potential to be used as an anti-cancer agent in the development of new treatment strategies in GBM.