BACKGROUND Pancreatic cancer is a very aggressive malignant disease due to lack of early diagnosis and chemotherapeutic resistance of the tumor cells. There is distinct evidence that food derived polyphenols possess chemopreventive effects in the development of several cancers including pancreatic carcinoma. Resveratrol, a phenolic compound found in grape skins and other fruits, is a nutraceutical with several therapeutic effects and known anticancer activity. The aim of the study is to analyze the expression of Wnt/β-catenin signaling pathway genes after treatment with resveratrol METHODS Human pancreatic cancer (PC) cell lines AsPC-1 and Capan-2 were purchased from Cell Lines Service (Germany), BxPC-3 from ATCC (VA, USA). AsPC-1 and Capan-2 carry KRAS mutations, while BxPC-3 and AsPC-1 are TP53 mutated. Resveratrol was obtained from Sigma (MO, USA). Cells were incubated for 72h with resveratrol at the indicated concentrations (50 e 100 μM) or with 0.11% DMSO vehicle (control). Cell viability was assessed by MTT assay. The mRNA expression of genes related to the Wnt/β-catenin pathway were detected by quantitative Real-Time PCR in triplicate. RESULTS We analyzed by MTT the effect of resveratrol on the viability of three PC cell lines. The drug significantly affected cell viability in a dose-dependent manner, with distinct sensitivities for the three cell lines. In AsPC-1, BxPC-3 and Capan-2 resveratrol showed IC50 values of 28.65 µM, 153.98 µM and 252.56 µM respectively. We also analyzed by Real-Time PCR the expression of Wnt/β-catenin signaling receptors (ROR and LPR6), trascription factor (LEF) and target (cyclin D1) genes in resveratrol-treated pancreatic cancer cell lines. Resveratrol inhibits Wnt/β-catenin signaling genes differently in the three cell lines. In particular the expression of LEF and cyclin D1 genes was considerably downregulated in AsPC-1 cell line compared to control. CONCLUSIONS These results demonstrate that resveratrol significantly inhibited cell viability in the PC cell lines in a dose-dependent manner. Furthermore we showed that resveratrol treatment reduces the expression of important and crucial genes of Wnt/β-catenin pathway. The two results together provides useful considerations to establish a new chemotherapeutic regimen for pancreatic cancer.

Effect of resveratrol on Wnt/ β-catenin signalling in pancreatic cancer cell lines

M. C. Curia;S. Veschi;R. Florio;L. De Lellis;Gitana Aceto;Alessandro Cama
2018

Abstract

BACKGROUND Pancreatic cancer is a very aggressive malignant disease due to lack of early diagnosis and chemotherapeutic resistance of the tumor cells. There is distinct evidence that food derived polyphenols possess chemopreventive effects in the development of several cancers including pancreatic carcinoma. Resveratrol, a phenolic compound found in grape skins and other fruits, is a nutraceutical with several therapeutic effects and known anticancer activity. The aim of the study is to analyze the expression of Wnt/β-catenin signaling pathway genes after treatment with resveratrol METHODS Human pancreatic cancer (PC) cell lines AsPC-1 and Capan-2 were purchased from Cell Lines Service (Germany), BxPC-3 from ATCC (VA, USA). AsPC-1 and Capan-2 carry KRAS mutations, while BxPC-3 and AsPC-1 are TP53 mutated. Resveratrol was obtained from Sigma (MO, USA). Cells were incubated for 72h with resveratrol at the indicated concentrations (50 e 100 μM) or with 0.11% DMSO vehicle (control). Cell viability was assessed by MTT assay. The mRNA expression of genes related to the Wnt/β-catenin pathway were detected by quantitative Real-Time PCR in triplicate. RESULTS We analyzed by MTT the effect of resveratrol on the viability of three PC cell lines. The drug significantly affected cell viability in a dose-dependent manner, with distinct sensitivities for the three cell lines. In AsPC-1, BxPC-3 and Capan-2 resveratrol showed IC50 values of 28.65 µM, 153.98 µM and 252.56 µM respectively. We also analyzed by Real-Time PCR the expression of Wnt/β-catenin signaling receptors (ROR and LPR6), trascription factor (LEF) and target (cyclin D1) genes in resveratrol-treated pancreatic cancer cell lines. Resveratrol inhibits Wnt/β-catenin signaling genes differently in the three cell lines. In particular the expression of LEF and cyclin D1 genes was considerably downregulated in AsPC-1 cell line compared to control. CONCLUSIONS These results demonstrate that resveratrol significantly inhibited cell viability in the PC cell lines in a dose-dependent manner. Furthermore we showed that resveratrol treatment reduces the expression of important and crucial genes of Wnt/β-catenin pathway. The two results together provides useful considerations to establish a new chemotherapeutic regimen for pancreatic cancer.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11564/706114
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