3-bromopyruvik asit ve EX527 'nin kombinasonunun pankreatik duktal adenokarsinom, MIAPACA-2 hücreleri üzerindeki sinercetistik etkisi

Since the mortality rate of pancreatic cancer in the world has been increasing and the chances of patient survival are 5 percent after diagnosis, it is almost impossible to treat after diagnosis, particularly in advanced stages. Because of its rapid progression to metastasis, it is difficult to determine the pathways of metabolic signals and determine which treatment strategy to perform. The aim of this study is to find the suitable treatment strategies to irreversibly kill pancreatic cancer cells as soon as they are diagnosed. In recent years, one of the strategies that have been developed for more effective and fast therapeutic nature of various anti-cancer drugs is to determine their suitable doses to be applied together in order to increase the overall efficiency. In the next years, co-treatment strategy will be increased to enhance the response of patients by restricting the metastatic progression through the inhibition of multi-direction signaling pathways, and so patients may survive longer and even ending their suffer from the disease. However, it is rather difficult to study metabolic metabolism because of the rapid progression of pancreatic cancer. One of the commonly used antiglycolytic agent, 3-bromopyruvic acid (3BP) has been demonstrated to be partly effective in interfering cancer metabolism. Recent studies have also shown that sirtuins are implied in the modulation of cellular metabolism under stress conditions through their activities, NAD+-dependent deacetylase or ADP-ribosyltransferase, which are related to cancer interference. The co-treatment of 3BP and the sirtuin-1 inhibitor, EX527, on pancreatic cancer cells was investigated. The application of these drugs together on pancreatic cells was found to be synergetic and their appropriate doses were optimized to investigate metabolic changes in pancreatic cancer cells. In addition, we have demonstrated affected metabolic pathways, which provided information for mitochondria-related death mechanisms.