Resveratrol induces AMPK-dependent MDR1 inhibition in colorectal cancer HCT116/L-OHP cells by preventing activation of NF-κB signaling and suppressing cAMP-responsive element transcriptional activity
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  • 作者:Ziyuan Wang ; Long Zhang ; Zhenhua Ni ; Jian Sun ; Hong Gao ; Zhuoan Cheng…
  • 关键词:Resveratrol ; Multi ; drug resistance ; AMPKα ; Colorectal cancer
  • 刊名:Tumor Biology
  • 出版年:2015
  • 出版时间:December 2015
  • 年:2015
  • 卷:36
  • 期:12
  • 页码:9499-9510
  • 全文大小:3,374 KB
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  • 作者单位:Ziyuan Wang (1)
    Long Zhang (1)
    Zhenhua Ni (1)
    Jian Sun (1)
    Hong Gao (1)
    Zhuoan Cheng (1)
    Jianhua Xu (1) (2)
    Peihao Yin (1)

    1. Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China
    2. Department of Clinical Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China
  • 刊物主题:Cancer Research;
  • 出版者:Springer Netherlands
  • ISSN:1423-0380
文摘
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-κB (NF-κB) activity, reduced phosphorylation levels of IκBα, and reduced nuclear translocation of the NF-κB 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 AMPKα 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-κB signaling and CREB activation in an AMPK-dependent manner. Keywords Resveratrol Multi-drug resistance AMPKα Colorectal cancer

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