Document Detail


Metformin reverses multidrug resistance in human hepatocellular carcinoma Bel‑7402/5‑fluorouracil cells.
MedLine Citation:
PMID:  25310259     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Metformin exhibits anti‑proliferative effects in tumor cells in vitro and in vivo. The present study investigated the ability of metformin to reverse multidrug resistance (MDR) in human hepatocellular carcinoma Bel‑7402/5‑fluorouracil (5‑Fu; Bel/Fu) cells. The synergistic anti‑proliferative effect of metformin combined with 5‑Fu was evaluated using a Cell Counting kit‑8 assay. The variation in apoptotic rates and cell cycle distribution were evaluated using a flow cytometric assay and variations in target gene and protein expression were monitored using reverse transcription‑polymerase chain reaction and western blot analysis. The results demonstrated that metformin had a synergistic anti‑proliferative effect with 5‑Fu in the Bel/Fu cells. The variations in the number of apoptotic cells and distribution of the cell cycle were consistent with the variability in cell viability. Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia‑inducible factor‑1α (HIF‑1α) and transcriptionally downregulated the expression of multidrug resistance protein 1/P‑glycoprotein (P‑gp) and multidrug resistance‑associated protein 1 (MRP1). Collectively, these findings suggested that metformin may target the AMPK/mTOR/HIF‑1α/P‑gp and MRP1 pathways to reverse MDR in hepatocellular carcinoma.
Authors:
Sunbin Ling; Yu Tian; Haiquan Zhang; Kaiqi Jia; Tingting Feng; Deguang Sun; Zhenming Gao; Fei Xu; Zhaoyuan Hou; Yan Li; Liming Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-08
Journal Detail:
Title:  Molecular medicine reports     Volume:  -     ISSN:  1791-3004     ISO Abbreviation:  Mol Med Rep     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-13     Completed Date:  -     Revised Date:  2014-10-14    
Medline Journal Info:
Nlm Unique ID:  101475259     Medline TA:  Mol Med Rep     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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