Inhibition of Amyloid Precursor Protein Processing Enhances Gemcitabine-mediated Cytotoxicity in Pancreatic Cancer Cells *

摘要: Pancreatic adenocarcinoma or pancreatic cancer is often diagnosed at a very late stage which point treatment options are minimal. Current chemotherapeutic interventions prolong survival marginally, thereby emphasizing the acute need for better to effectively manage this disease. Studies from different laboratories have shown that Alzheimer disease-associated amyloid precursor protein (APP) overexpressed in various cancers but its significance not known. Here we sought determine role of APP cell and proliferation. Our results show cells secrete high levels sAPPα, α-secretase cleaved ectodomain fragment APP, as compared with normal non-cancerous cells. Treatment batimastat GI254023X, inhibitors ADAM10, prevented sAPPα generation reduced survival. Additionally, inhibition significantly anchorage independent growth The effect on colony formation was enhanced when downregulation combined gemcitabine treatment. Moreover, batimastat-treated recombinant reversed inhibitory drug indicating can indeed induce proliferation Down-regulation ADAM10 brought about similar results, did treatment, confirming processing important these These suggest might enhance effectiveness existing regimen outcome.