Gene Gpx3 With Pancreatic Cancer Chemotherapy Resistance-associated Sexual Experimental Research

Drug resistance, which influences chemotherapeutic effect of pancreatic cancers,is one of the major issues in cancer chemotherapy. In the last decades, it is indicatedthat reactive oxygen species (ROS) may play an important role in drug resistance.ROS are oxygen-containing chemical species with highly reactive chemicalproperties, usually including H₂O₂, superoxide (O₂^-·), and hydroxyl radicals (OH·).Intracellular accumulation of ROS is proved to be cytotoxic, while whetherintracellular ROS induce or reduce drug resistance of tumor is still argued.Intracellular ROS are scavaged by antioxidant enzymes. There are three majortypes of antioxidant enzymes in mammalian cells: SOD, catalase and peroxidase, ofwhich glutathione peroxidases (GPXs) are the most prominent. GPXs areubiquitously expressed proteins which catalyze in the reduction of hydrdrogenperoxides and organichydroperoxides by glutathione. By eliminating intracellularperoxide, GPXs protect cells from oxidative free radicals impairments. There areseveral isforms which differ in their primary structure and localization. GPX3 is anextracellular type, which is mainly expressed by the kidney and then released into theblood.According to our previous study by gene array, the expression of Gene GPX3may be closely related to the drug resistance of pancreatic cancer.In this study, we detected the expression of GPX3 in four human pancreaticcancer cell lines: SW1990, SW1990/FU, SW1990/ADM and SW1990/GEM. Thelast three, which are named as SW1990/drugs, are resistant to 5-FU, ADM and GEMrespectively. Compared with SW1990, both mRNA level and protein level of GPX3is higher in SW1990/Drugs, which indicates over-expression of GPX3 in bothtransduction and translation levels.Then we apply siRNA transfection to down-regulate expression of GPX3. Intransfected cells, mRNA and protein levels of GPX3 depress, with noticeable decrease of drug resistance of certain chemical drugs, measured by IC₅₀.In conclusion, expression level of GPX3 in human pancreatic cancer cell linesis closely related to drug-resistance. We also indicate that GPX3, as a secretoryproteins, is expressed in human pancreatic tumor cell.