Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology*
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Animals
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Blotting, Western
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Cell Line
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Cell Proliferation / drug effects
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Chickens
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Cholecalciferol / pharmacology*
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Chorioallantoic Membrane / drug effects
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Chorioallantoic Membrane / metabolism
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Embryo, Mammalian / cytology
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Embryo, Mammalian / drug effects
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Embryo, Mammalian / metabolism
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Hedgehog Proteins / antagonists & inhibitors
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Hedgehog Proteins / metabolism*
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Humans
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Mice
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Mice, Inbred NOD
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Mice, Knockout
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Mice, SCID
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Pancreatic Neoplasms / drug therapy
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology*
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Receptors, Calcitriol / physiology
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Receptors, G-Protein-Coupled / antagonists & inhibitors
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Receptors, G-Protein-Coupled / metabolism*
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Signal Transduction
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Smoothened Receptor
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Xenograft Model Antitumor Assays*
Substances
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Hedgehog Proteins
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Receptors, Calcitriol
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Receptors, G-Protein-Coupled
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SMO protein, human
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Smoothened Receptor
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Cholecalciferol