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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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