Assessing the efficacy of the hedgehog pathway inhibitor vitamin D3 in a murine xenograft model for pancreatic cancer.

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.

• Authors: Lois W Brüggemann, Karla C S Queiroz, Khatera Zamani, Amber van Straaten, C Arnold Spek, Maarten F Bijlsma
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 10 Issue 1 Pg. 79-88 (Jul 01 2010) ISSN: 1555-8576 [Electronic] United States
• PMID: 20495364 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hedgehog Proteins
• Receptors, Calcitriol
• Receptors, G-Protein-Coupled
• SMO protein, human
• Smoothened Receptor
• Cholecalciferol

Topics

• Adenocarcinoma (drug therapy, metabolism, pathology)
• Animals
• Blotting, Western
• Cell Line
• Cell Proliferation (drug effects)
• Chickens
• Cholecalciferol (pharmacology)
• Chorioallantoic Membrane (drug effects, metabolism)
• Embryo, Mammalian (cytology, drug effects, metabolism)
• Fibroblasts (cytology, drug effects, metabolism)
• Hedgehog Proteins (antagonists & inhibitors, metabolism)
• Humans
• Mice
• Mice, Inbred NOD
• Mice, Knockout
• Mice, SCID
• Pancreatic Neoplasms (drug therapy, metabolism, pathology)
• Receptors, Calcitriol (physiology)
• Receptors, G-Protein-Coupled (antagonists & inhibitors, metabolism)
• Signal Transduction
• Smoothened Receptor
• Xenograft Model Antitumor Assays