| Abstract [eng] |
Pancreatic cancer is the seventh most common cancer in the world. However, it places fourth according to mortality rates. Delayed diagnosis and resistance to chemotherapeutics are the main causes of such a poor outcome. Thus, new combination therapies and new ways to induce cell death are constantly under development. The works of this dissertation aimed to find the anticancer potential and to elucidate the mechanisms of two strategies – iron-dependent cell death ferroptosis and starvation induction. The results showed that sensitivity to ferroptosis can be mediated by growth factor, amino acid L-glutamine, L-lysine and L-arginine deprivation and mTORC1 inhibition with rapamycin. It was shown that in starved pancreatic cancer cells, sensitivity to ferroptosis is mediated by kinases ERK1/2 and JNK. Moreover, in this dissertation, a new pancreatic cancer cell line Capan-26 was established and characterized in vitro. This is the first pancreatic cancer cell line derived from a tumor of a Lithuanian patient. In this unique and a commercial cell line growth factor deprivation correlated with sensitivity to ferroptosis inducer erastin. With this in mind, several EMT targeting compounds were evaluated for their effects on cell sensitivity to erastin and new effective combinations of erastin and EMT-modulating compounds were discovered. |
