國家衛生研究院 NHRI:Item 3990099045/13284
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    題名: Metformin resensitizes sorafenib-resistant HCC cells through AMPK-dependent autophagy activation
    作者: Lai, HY;Tsai, HH;Yen, CJ;Hung, LY;Yang, CC;Ho, CH;Liang, HY;Chen, FW;Li, CF;Wang, JM
    貢獻者: National Institute of Cancer Research
    摘要: Despite the activation of autophagy may enable residual cancer cells to survive and allow tumor relapse, excessive activation of autophagy may eventually lead to cell death. However, the details of the association of autophagy with primary resistance in hepatocellular carcinoma (HCC) remain less clear. In this study, cohort analysis revealed that HCC patients receiving sorafenib with HBV had higher mortality risk. We found that high epidermal growth factor receptor (EGFR) expression and activity may be linked to HBV-induced sorafenib resistance. We further found that the resistance of EGFR-overexpressed liver cancer cells to sorafenib is associated with low activity of AMP-activated protein kinase (AMPK) and CCAAT/enhancer binding protein delta (CEBPD) as well as insufficient autophagic activation. In response to metformin, the AMPK/cAMP-response element binding protein (CREB) pathway contributes to CEBPD activation, which promotes autophagic cell death. Moreover, treatment with metformin can increase sorafenib sensitivity through AMPK activation in EGFR-overexpressed liver cancer cells. This study suggests that AMPK/CEBPD-activated autophagy could be a potent strategy for improving the efficacy of sorafenib in HCC patients.
    日期: 2021-01
    關聯: Frontiers in Cell and Developmental Biology. 2021 Jan 21;8:Article number 596655.
    Link to: http://dx.doi.org/10.3389/fcell.2021.596655
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2296-634X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000614399700001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85100477339
    顯示於類別:[其他] 期刊論文

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