Identification of the effects of metformin on the laryngeal cancer hep-2 cells and investigation of its synergistic impacts with 5-fluorouracil

Larynx cancer (LCa) is the most common head and neck cancer and accounts for 1-2.5% of all human cancers worldwide. Despite development of novel diagnostic and therapeutic tools for LCa, there has been no significant reduction in the 5-year survival rate over the past 30 years. 5-FU is a widely used chemotherapeutic agent in the treatment of LCa, however, it did not contribute much to the LKa patients' overall survival. Metformin is an oral anti-diabetic drug widely used in the treatment of Type 2 diabetes and has been recently shown to have anti-cancer activity in a variety of cancer types. There are several studies in the literature that suggest that metformin might sensitize the cancer cells to chemotherapeutic drugs. There is also evidence that metformin might have anti-proliferative potential on the human LCa cell line Hep-2 cells. In this thesis, it is aimed at exploring the anti-cancer effects of metformin alone and in combination with 5-FU on Hep-2 cells. When Hep-2 cells are treated with metformin alone, it inhibited cell proliferation by inducing apoptosis and suppressed cell migration in Hep-2 cells. Besides, metformin and 5-FU synergistically induced apoptosis in cells, while inhibiting cell proliferation and migration. Unexpectedly, metformin was found to enhance cellular invasion and reverse the inhibitory effect of 5-FU on the invasive potential of Hep-2 cells. To the best of our knowledge, our findings suggest for the first time in the literature, that metformin can be used as an adjuvant agent in the treatment of LCa. However, the potential of metformin to promote the invasion of cancer cells should not be neglected.