NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment

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 d...

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Autores principales:	North WG, Liu F, Lin LZ, Tian R, Akerman B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	pancreatic cancer NMDA receptors inhibitors potential therapy Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2d238f069895435bbb68285a2557a1cb
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spelling	oai:doaj.org-article:2d238f069895435bbb68285a2557a1cb2021-12-02T03:08:32ZNMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment1179-1438https://doaj.org/article/2d238f069895435bbb68285a2557a1cb2017-07-01T00:00:00Zhttps://www.dovepress.com/nmda-receptors-are-important-regulators-of-pancreatic-cancer-and-are-p-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438William 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 therapyNorth WGLiu FLin LZTian RAkerman BDove Medical Pressarticlepancreatic cancerNMDA receptorsinhibitorspotential therapyTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol Volume 9, Pp 79-86 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	pancreatic cancer NMDA receptors inhibitors potential therapy Therapeutics. Pharmacology RM1-950
spellingShingle	pancreatic cancer NMDA receptors inhibitors potential therapy Therapeutics. Pharmacology RM1-950 North WG Liu F Lin LZ Tian R Akerman B NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment
description	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
format	article
author	North WG Liu F Lin LZ Tian R Akerman B
author_facet	North WG Liu F Lin LZ Tian R Akerman B
author_sort	North WG
title	NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment
title_short	NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment
title_full	NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment
title_fullStr	NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment
title_full_unstemmed	NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment
title_sort	nmda receptors are important regulators of pancreatic cancer and are potential targets for treatment
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/2d238f069895435bbb68285a2557a1cb
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_version_	1718401908327055360

NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment

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