期刊
TUMOR BIOLOGY
卷 36, 期 12, 页码 9499-9510出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-015-3636-3
关键词
Resveratrol; Multi-drug resistance; AMPK alpha; Colorectal cancer
类别
资金
- National Natural Science Foundation of China [81473482]
- Putuo District Committee of Science and Technology, Shanghai, China [201102]
- Xinglin Scholars of Shanghai University of Traditional Chinese Medicine
- construct program of the key discipline of State Administration of Traditional Chinese Medicine of the People's Republic of China
Resveratrol, a natural polyphenolic compound found in foods and beverages, has attracted increasing attention in recent years because of its potent chemopreventive and anti-tumor effects. In this study, the effects of resveratrol on the expression of P-glycoprotein/multi-drug resistance protein 1 (P-gp/MDR1), and the underlying molecular mechanisms, were investigated in oxaliplatin (L-OHP)-resistant colorectal cancer cells (HCT116/L-OHP). Resveratrol downregulated MDR1 protein and mRNA expression levels and reduced MDR1 promoter activity. It also enhanced the intracellular accumulation of rhodamine 123, suggesting that resveratrol can reverse multi-drug resistance by downregulating MDR1 expression and reducing drug efflux. Resveratrol treatment also reduced nuclear factor-kappa B (NF-kappa B) activity, reduced phosphorylation levels of I kappa B alpha, and reduced nuclear translocation of the NF-kappa B subunit p65. Moreover, downregulation of MDR1 expression and promoter activity was mediated by resveratrol-induced AMP-activated protein kinase (AMPK) phosphorylation. The inhibitory effects of resveratrol on MDR1 expression and cAMP-responsive element-binding protein (CREB) phosphorylation were reversed by AMPK alpha siRNA transfection. We found that the transcriptional activity of cAMP-responsive element (CRE) was inhibited by resveratrol. These results demonstrated that the inhibitory effects of resveratrol on MDR1 expression in HCT116/L-OHP cells were closely associated with the inhibition of NF-kappa B signaling and CREB activation in an AMPK-dependent manner.
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