Akademik Veri Yönetim Sistemi
10. Uluslararası Bilimsel Araştırmalar Kongresi, Adana, Türkiye, 2 - 04 Nisan 2023, ss.326-327
Ovarian cancer is a fatal type of cancer in women. The most substantial factor responsible for
deaths in ovarian cancer is multidrug resistance caused by traditional chemotherapeutics or new
targeted agents, and tumor recurrence caused by resistance. One of the most significant
mechanisms in the development of drug resistance against many chemotherapeutics, especially
paclitaxel, is the increased expression of ABCB1/MDR1 protein which is a member of the ABC
transporter protein family in ovarian cancer. As there is currently no approved and effective
treatment for multidrug resistance and tumor recurrence, therapeutic approaches that can
reverse drug resistance need to be explored to improve chemotherapy efficacy in ovarian
cancer. Therefore, the construction of an in vitro model for cancer resistance in cell lines that
allow these studies to be investigated at the in vitro grade before proceeding to clinical studies
comes to the fore as a very significant issue. In this study, it is aimed to perform an in vitro
model for preclinical research that will allow the development of candidate inhibitor molecules
or therapeutic agents for drug resistance in cancer. In this context, A2780 cells were cultured
in medium containing paclitaxel for six months by exposure to various concentrations of
paclitaxel ranging from 10 picomolar to 50 nanomolar. The initial concentration used in the
resistance protocols was determined with the aid of the half-maximal inhibitory concentration
(IC50) of paclitaxel in a sensitive A2780 ovarian cancer cell line. A2780 cells were rendered
resistant to paclitaxel and drug resistance developed in sensitive cells was demonstrated by
comparing IC50 values in sensitive and resistant cells. Second, the expression of the MDR1
gene, which is known to be associated with resistance to paclitaxel, was confirmed by qPCR
analysis. In the results obtained, the IC50 value of paclitaxel-resistant A2780 cells was
255.2183 nM, while the IC50 value of sensitive A2780 cells was determined as 57.5753 nM.
In addition, paclitaxel-resistant A2780 cells had 768,167-fold higher MDR1 expression than
sensitive A2780 cells. It was confirmed that in vitro cancer drug resistance model was
established due to increased expression of MDR1 protein in A2780 cells within the scope of
these results.