Li-Shu Wang
Medical College of Wisconsin, USA
Title: Black raspberries inhibit pancreatic carcinogenesis via suppressing Raf/ MEK/ ERK/ STAT3 signaling pathways and promoting apoptosis
Biography
Biography: Li-Shu Wang
Abstract
Although with improved understanding of the pathophysiology of pancreatic ductal adeno-carcinoma (PDAC) in the past two decades, PDAC remains one of the poorest prognostic tumors, with an extremely low 5-year survival rate (4.1%). Diets rich in fruits and vegetables have been reported to reduce the risk of cancer development. Our current study investigated the potential effects of BRBs against PDAC in mice. KrasLSL.G12D/+-Trp53LSL.R172H/+-Pdx-1-Cre mice spontaneously develop PDAC that recapitulates human PDAC. Four-week-old KrasLSL.G12D/+-Trp53LSL.R172H/+-Pdx-1-Cre mice bearing precancerous pancreatic intraepithelial neoplasia (PanIN) lesions were fed either control or 5% BRB diet. Kaplan-Meier survival analysis showed that BRBs significantly prolonged survival of PDAC mice. BRBs suppressed Raf/MEK/ERK/STAT3 pathways, downstream of Kras and inhibited cell proliferation in pancreatic tumors. In addition, BRBs significantly decreased the size of tumors produced by injecting luciferase-transfected human Panc-1 cells (Panc-1-Luc) into the pancreas of NOD.SCID mice. Orthotopic tumors in BRB-treated NOD.SCID mice had higher rate of apoptosis compared to tumors from mice fed control diet. These results support the hypothesis of a clinical potential of BRBs for the delay of pancreatic cancer progression through suppressing cancer cell proliferation and/or promoting apoptosis.