Metformin Resensitizes Sorafenib-Resistant HCC Cells Through AMPK-Dependent Autophagy Activation

doi:10.3389/fcell.2020.596655

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/34489

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/34489

Title:	Metformin Resensitizes Sorafenib-Resistant HCC Cells Through AMPK-Dependent Autophagy Activation
Authors:	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
Contributors:	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
Keywords:	sorafenib metformin autophagy AMPK CEBPD
Date:	2021
Issue Date:	2023-11-11 11:57:04 (UTC+8)
Publisher:	FRONTIERS MEDIA SA
Abstract:	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.
Relation:	FRONT CELL DEV BIOL, v.9, 596655
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles [Dept. of Health and Nutrition (including master's program)] Periodical Articles

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