Rutenyum komplekslerinin ovaryum kanseri üzerindeki etkisi

Ovarian cancer has a high death incidence among females worldwide. Although first line chemotherapy with platinum/taxane combination has been used successfully in ovarian cancer, the majority of the patients relapsed and gained chemotherapy resistance. Lately, ruthenium complexes have emerged as encouraging chemotherapeutic agents to replace the platinum-based chemotherapy regarding their selective mechanisms of action along with lower toxicity, and the potential to overcome chemotherapy resistance. It is accepted that cancer is a heterogeneous disease, and it also exhibits characteristic variations in metabolic phenotype from one cell to another. Because cancer cells repeatedly reprogram to adapt to challenging environmental changes. In this thesis, we aimed to examine the effects of chemotherapeutic agents on ovarian cell lines. Therefore, we evaluated the alterations in the levels of glycolysis metabolites such as glucose, pyruvate; critical intermediates of TCA cycle such as OAA, αKG, succinate, fumarate, malate, and the metabolite of anaerobic respiration, lactate, with respect to the Ru, PAX, CAR concentrations and incubation time. The results proved that each ovarian cell line displayed distinct metabolic phenotypes of energy, and thus, each ovarian cell line responded in a unique way to chemotherapeutic agents. Additionally, ruthenium complexes showed better anti-tumor activity than carboplatin and lower toxicity against healthy cells than paclitaxel. Among ruthenium agents, complex 1a demonstrated the most promising results against cisplatin-resistant ovarian cancer cells.