Metformin reverses multidrug resistance in human hepatocellular carcinoma Bel‑7402/5‑fluorouracil cells Corrigendum in /10.3892/mmr.2022.12691

Ling,Sunbin; Tian,Yu; Zhang,Haiquan; Jia,Kaiqi; Feng,Tingting; Sun,Deguang; Gao,Zhenming; Xu,Fei; Hou,Zhaoyuan; Li,Yan; Wang,Liming

doi:10.3892/mmr.2014.2614

Metformin reverses multidrug resistance in human hepatocellular carcinoma Bel‑7402/5‑fluorouracil cells

Corrigendum in: /10.3892/mmr.2022.12691

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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Affiliations: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Department of Intergrative Medicine, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
Published online on: October 8, 2014 https://doi.org/10.3892/mmr.2014.2614
Pages: 2891-2897
Copyright: © Ling et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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.

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