Aurelija Maziukienė, Aldona Jakštaitė, Giedrė Šilkūnienė, Kristina Kmieliūtė, Antanas Gulbinas, Žilvinas Dambrauskas
Pancreatic adenocarcinoma is one of the most aggressive human malignancies with high mortality rates. Low survival rates are due to late diagnosis at advanced stages of the disease. High invasiveness and chemoresistance of pancreatic adenocarcinoma at least partially could be related to the antiapoptotic activity of intracelular ROS generated by Nox4. There are only few studies about Nox4 expression in pancreatic cancer, yet Nox4 is believed to be relevant antiapoptotic factor in pancreatic cancer cells. In this study we have determined the expression of Nox4 in human pancreatic tissue at both protein and mRNA levels. We compared how Nox4 is overexpressed in pancreatic cancer in comparison to human healthy adjacent and healthy donor pancreatic tissue. We have also identified the effect of ROS formation in MiaPaca-2 and Capan-2 cells under treatment with NADPH oxidase inhibitors DPI and apocynin. Our results showed that DPI and apocynin inhibited ROS formation. Moreover, it decreased viability of pancreatic cancer cells and induced apoptosis as well. Result confirms ROS being responsible for antiapoptotic activity of pancreatic cancer cells. These findings point out to NADPH oxidases being a potential terapeutic targets in treatment of cancer.
Keyword(s): pancreatic adenocarcinoma; NOX4; ROS
Full Text: PDF