Abstract B59: Black raspberries inhibit pancreatic carcinogenesis by suppressing Raf/MEK/ERK/STAT3 signaling pathways and promoting apoptosis

Autor: Chad W. Skaer, Li-Shu Wang, Kiyoko Oshima, Pan Pan, Hsin-Tzu Wang, Yi-Wen Huang, Susan Tsai
Rok vydání: 2016
Předmět:
Zdroj: Cancer Research. 76:B59-B59
ISSN: 1538-7445
0008-5472
Popis: Background: Despite improved understanding of the pathophysiology of pancreatic ductal adenocarcinoma (PDAC) in the past two decades, PDAC has an extremely low 5-year survival rate (7%). However, diets rich in fruits and vegetables have been reported to reduce the risk of cancer development. We previously demonstrated that black raspberries (BRBs) have chemopreventive effects in human colorectal cancer patients and mouse models of colorectal cancer. Our current study aimed to investigate the potential effects of BRBs against PDAC in mice. Methods: Mice that carry a constitutively activated KrasLSL.G12D/+ oncogene and loss-of-function Trp53LSL.R172H/+ tumor-suppressor gene in the pancreas (KrasLSL.G12D/+-Trp53LSL.R172H/+-Pdx-1-Cre) spontaneously develop PDAC that recapitulates the human PDAC. Four-week-old KrasLSL.G12D/+-Trp53LSL.R172H/+-Pdx-1-Cre mice were given a control diet or a control diet supplemented with 5% BRBs. In addition, luciferase-transfected human Panc-1 (Panc-1-Luc) cells were orthotopically injected into the pancreas of nonobese, diabetic, severe combined immunodeficient (NOD.SCID) mice. Four weeks after the inoculation of Panc-1-Luc cells, the NOD.SCID mice were given a control diet or a control diet supplemented with 5% BRBs for 6 weeks. Gross tumor volume of orthotopic pancreatic tumors was measured. Results: The 4-week-old KrasLSL.G12D/+-Trp53LSL.R172H/+-Pdx-1-Cre mice developed pancreatic intraepithelial neoplasia (PanIN) lesions, which are the precancerous lesions of PDAC, and they were fed control or 5% BRB diet. Kaplan-Meier survival analysis showed that 5% BRBs significantly prolonged the survival of those PDAC mice with a median survival of 189 days versus 154 days for the mice fed the control diet. Molecular studies suggested that 5% BRBs suppress the Raf/MEK/ERK/STAT3 pathway, which is the downstream of Kras activation, and inhibit cancer cell proliferation in pancreatic tumor tissues. In addition, 5% BRBs significantly decreased the gross tumor volume of orthotopic tumors produced by injecting Panc-1-Luc cells into the pancreas. Orthotopic pancreatic tumors in BRB-treated NOD.SCID mice had a higher rate of apoptosis than tumors from mice fed the control diet. Conclusions: These results support the hypothesis that BRBs have the clinical potential to delay pancreatic cancer progression by suppressing cancer cell proliferation and/or promoting apoptosis. Citation Format: Pan Pan, Chad W. Skaer, Hsin-Tzu Wang, Susan Tsai, Kiyoko Oshima, Yi-Wen Huang, Li-Shu Wang.{Authors}. Black raspberries inhibit pancreatic carcinogenesis by suppressing Raf/MEK/ERK/STAT3 signaling pathways and promoting apoptosis. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B59.
Databáze: OpenAIRE
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