Clinical Pharmacology: Advances and Applications (Jul 2017)
NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment
Abstract
William G North,1,2 Fuli Liu,1 Liz Z Lin,1 Ruiyang Tian,2 Bonnie Akerman1 1Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth College, 2Woomera Therapeutics Inc, Lebanon, NH, USA Abstract: Pancreatic cancer, particularly adenocarcinoma of the pancreas, is a common disease with a poor prognosis. In this study, the importance of N-methyl-D-aspartate (NMDA) receptors for the growth and survival of pancreatic cancer was investigated. Immunohistochemistry performed with antibodies against GluN1 and GluN2B revealed that all invasive adenocarcinoma and neuroendocrine pancreatic tumors likely express these two NMDA receptor proteins. These proteins were found to be membrane components of pancreatic cancer cell lines, and both channel-blocker antagonist and GluN2B antagonist significantly reduced cell viability in vitro. Both types of antagonists caused an internalization of the receptors. Dizocilpine maleate (MK-801) and ifenprodil hemitartrate both significantly inhibited the growth of pancreatic tumor xenografts in nu/nu mice. These findings predict that, as for other solid tumors investigated by us, pancreatic cancer could be successfully treated, alone or in combination, with NMDA receptor antagonists or other receptor-inhibiting blocking agents. Keywords: pancreatic cancer, NMDA receptors, inhibitors, potential therapy
