Assessing the efficacy of the hedgehog pathway inhibitor vitamin D3 in a murine xenograft model for pancreatic cancer.
The developmental Hedgehog (Hh) pathway has been shown to cause malignancies in the adult organism, specifically in the proximal gastrointestinal tract. Previous studies have used the Hh-inhibitory alkaloid cyclopamine to treat Hh-dependent tumor growth. The present study aimed to determine the efficacy and specificity of the recently discovered endogenous inhibitor of the Hh pathway, vitamin D3, on inhibition of pancreatic adenocarcinoma cell growth in vitro and in vivo. Vitamin D3 was found to inhibit cell growth specifically through inactivation of Smo and the downstream Hh pathway, rather than activation of the vitamin D3 receptor. However, in in vivo models vitamin D3 was not found to be effective against tumor cell growth.
Brüggemann
Lois W
LW
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Queiroz
Karla C S
KC
Zamani
Khatera
K
van Straaten
Amber
A
Spek
C Arnold
CA
Bijlsma
Maarten F
MF
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D002762:Cholecalciferol / Q000494:pharmacology*; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018167:Receptors, Calcitriol / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D000072086:Smoothened Receptor; D023041:Xenograft Model Antitumor Assays
D053823:Hedgehog Proteins; D018167:Receptors, Calcitriol; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; D002762:Cholecalciferol