Document Detail

Metformin reverses multidrug resistance in human hepatocellular carcinoma Bel‑7402/5‑fluorouracil cells.
MedLine Citation:
PMID:  25310259     Owner:  NLM     Status:  Publisher    
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.
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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