Oncology Medical News about pancreatic cancer;prevention;beta-blocker;propranolol

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Prevention of pancreatic cancer by the beta-blocker propranolol
Anti-Cancer Drugs, 07/02/09

Al-Wadei H et al. - In a trial to examine whether propranolol prevents development of pancreatic ductal adenocarcinoma (PDAC) induced in hamsters with ethanol-induced pancreatitis by nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), it appears that increased cAMP signaling is an important factor that drives development and progression of PDAC and that inhibition of cAMP formation is a promising new target for prevention and adjuvant therapy of PDAC.

Methods

This study investigates whether propranolol prevents development of PDAC induced in hamsters with ethanol-induced pancreatitis by NNK.

Results

Propranolol had strong cancer preventive effects in this animal model.
Western blots of pancreatic duct cells and PDAC cells harvested by laser capture microscopy showed significant upregulation of the α7 nAChR associated with significant inductions of p-CREB, p-ERK1/2, and increases in epidermal growth factor and vascular endothelial growth factor in PDAC cells of hamsters not treated with propranolol.
These effects were reversed by treatment with propranolol.
These data suggest that propranolol may prevent development of PDAC by blocking cAMP-dependent intracellular signaling, cAMP-dependent release of epidermal growth factor, and PKA-dependent release of vascular endothelial growth factor, while additionally downregulating the α7 nAChR by inhibiting cAMP-mediated subunit assembly.
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