The Effect of Epigallocatechin Gallate on MicroRna Levels in Pancreatic Cancer Cells
Project no. 20764 · Status: Kapanmış · 2019
Summary
Pancreatic cancer is one of the leading causes of cancer deaths in developed countries, it is known as one of the deadliest malignant neoplasms in the world. The 5-year median survival rate for pancreatic cancer has been shown to be less than 5%. The incidence of pancreatic cancer has been increasing day by day. Although its symptoms are rather vague, involvement occurs in the head, trunk or tail of the pancreas. Weight loss, pain in the stomach area and jaundice have been reported as early symptoms.Innovative approaches are being put forward every day to develop new methods that will provide early diagnosis and treatment of pancreatic cancer. Recently, studies related to miRNA expression changes have started after it has been thought that one of the reasons that pancreatic cancer progresses without showing any symptoms may be dynamic miRNA regulation as a result of genetic mutations. MicroRNAs (miRNAs) are 18 to 22 nucleotides in length, single-stranded, non-coding RNAs that regulate important biological processes including response to cellular stressors such as differentiation, proliferation, hypoxia, nutrient depletion. miRNAs in cancer tissue and serum have been defined in pancreatic cancer to identify potential therapeutic targets, to understand the pathways involved in tumorigenesis, and to define prognostic tumor signatures. The fact that tissue removal from pancreatic cancer is an invasive method is an obstacle in early diagnosis of pancreatic cancer patients. Considering in detail in studies with many miRNA signatures found in pancreatic tissue and peripheral blood and pathways associated with pancreatic cancer, three miRNA biomarkers (miR21, miR155 and miR200) have been identified in both cancer tissue and blood. These miRNAs have been found to be regulated by central genetic and epigenetic changes in some genes including p53, TGF-ß, p16INK4A, BRCA1 / 2, and KRAS which has been frequently observed in pancreatic cancer Gemcitabine (GEM) is a pyrimidine antimetabolite commonly used in the treatment of pancreatic cancer. Since GEM targets all dividing cells, serious side effects occur in 10% of pancreas patients who use GEM during treatment, and healthy cells are also affected. Therefore, GEM combined with other active compounds has increased the 1-year survival of patients with pancreatic cancer has been shown in meta-analysises. Catechin, one of flavanols, constitutes the most important polyphenol group in tea. Catechins, among the polyphenols in tea, constitute 30% of the dry leaf weight. Among them, EGCG is the main polyphenol and constitutes 60% of the total catechins. The effect of (-) - Epigallocatechin-3-gallate (C22H18O11), the active compound of green tea (Camellia sinensis), on pancreatic cancer has been studied in many studies. But, extensive studies about the therapeutic potential of EGCG on miRNAs in pancreatic cancer have not been conducted. In this study, it is aimed to determine the cytotoxic and apoptotic effects of EGCG, Gemcitabin and their combination in PANC1 cells, referred as pancreatic cancer model, in order to increase of therapeutic efficacy of Gemcitabine, and then to investigate the effect of this combination on miRNA expression levels that play a role in cancer progression. The cytotoxicity of Gemcitabine and EGCG in pancreatic cancer cells will be determined by the mono-therapy and combination treatment, and whether they have a synergistic effect will be determined. In addition, target-specific treatment alternatives for the disease will be developed by means of determining the effects of these active compound as single- or combined-treatment on changes in the expression levels of miRNAs associated with apoptosis and cancer, and our findings will be a significant contribution to the literature.