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    標題: Metformin Resensitizes Sorafenib-Resistant HCC Cells Through AMPK-Dependent Autophagy Activation
    作者: Lai, Hong-Yue
    Tsai, Hsin-Hwa
    Yen, Chia-Jui
    Hung, Liang-Yi
    Yang, Ching-Chieh
    Ho, Chung-Han
    Liang, Hsin-Yin
    Chen, Feng-Wei
    Li, Chien-Feng
    Wang, Ju-Ming
    貢獻者: Natl Cheng Kung Univ, Coll Biosci & Biotechnol, Dept Aotechnol & Bioind Sci
    Chi Mei Med Ctr, Dept Med Res
    Chi Mei Med Ctr, Dept Pathol
    Natl Cheng Kung Univ Hosp, Dept Oncol
    Natl Cheng Kung Univ, Coll Med
    Kaohsiung Med Univ, Coll Med, Grad Inst Med
    Chi Mei Med Ctr, Dept Radiat Oncol
    Chia Nan Univ Pharm & Sci, Dept Pharm
    Chia Nan Univ Pharm & Sci, Dept Hosp & Hlth Care Adm
    Natl Cheng Kung Univ, Int Ctr Wound Repair & Regenerat
    Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci
    Natl Hlth Res Inst, Natl Inst Canc Res
    Kaohsiung Med Univ, Inst Clin Med
    Southern Taiwan Univ Sci & Technol, Dept Biotechnol, Tainan, Taiwan;[Wang, Ju-Ming
    Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Med Sci
    關鍵字: sorafenib
    metformin
    autophagy
    AMPK
    CEBPD
    日期: 2021
    上傳時間: 2023-11-11 11:57:04 (UTC+8)
    出版者: FRONTIERS MEDIA SA
    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.
    關聯: FRONT CELL DEV BIOL, v.9, 596655
    顯示於類別:[藥學系(所)] 期刊論文
    [保健營養系(所) ] 期刊論文

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