Deguelin's contribution to standard therapy in an experimental lung cancer model
2021
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Advisor: Prof. Dr. Gül Hüray İşlekel
Abstract (EN)
Although the treatment of cancer is difficult despite intense efforts, its prevention is also difficult and important. Due to the fact that the struggle is so intense and high, unfortunately, cancer is the leading cause of death worldwide. Lung cancer, on the other hand, ranks first among cancer-related deaths in the world, regardless of gender. The most effective chemotherapeutic agents used in the treatment of cancer are toxic to normal tissues and the incidence of side effects is therefore high. Therefore, there is a need for new drugs and regimen methods with no or minimal therapeutic or preventative effects. This study hypothesized that Deguelin has an effective concentration inhibitory effect on the proliferation of cancer cells in an in vitro and in vivo lung cancer model, and that the effect of the [DEG + DTX] / 2 combination to reduce lung cancer cells and tumor volume can also be successful compared to the use of drugs separately. IK50 doses were determined by investigating the cytotoxic effects of Docetaxel and Deguelin alone in LLC cell lines. The determined effective concentrations of Deguelin, Docetaxel and their combinations were applied to the LLC cells. Flow cytometric analysis (for apoptosis, cell cycle), migration analysis, and 3D angiogenesis (tubular formation) methods were performed using cell cultures. The anti-cancer, apoptotic and anti-angiogenic effects of DEG, DTX, and their combinations were investigated in an in vivo model of syngeneic lung cancer on C57BL / 6 mice with the LLC cell line, which was an important step of this study. In our study, although the DEG + DTX combination was more successful in suppressing cell proliferation than single use of drugs in the in vitro experimental model, this success in tumor volume, apoptosis markers, and angiogenesis gene expression levels in the in vivo experimental model turned in favor of single therapy. As a result, it is concluded that the combination dose should be re-evaluated or the time frame in the treatment regimen should be adjusted differently for the combination dose. Deguelin's anticancer effect may be through reducing the proliferation of cancer cells and tumor spread.
Author
Dr. Hakan Cengiz
Institution
How to Cite
Hakan Cengiz (Doctorate thesis). Deguelin's contribution to standard therapy in an experimental lung cancer model, 2021, Dokuz Eylül University.
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