Tumor Biology

, Volume 36, Issue 4, pp 2957–2964 | Cite as

Metformin sensitizes hepatocellular carcinoma to arsenic trioxide-induced apoptosis by downregulating Bcl2 expression

  • Xuejun Yang
  • Deguang Sun
  • Yu Tian
  • Sunbin Ling
  • Liming Wang
Research Article

Abstract

Hepatocellular carcinoma (HCC) is a highly malignant tumor that can evolve rapidly to acquire resistance to conventional chemotherapies. Arsenic trioxide (ATO) is a traditional Asian medicine, and a phase II study has shown that treatment with ATO alone was not effective against HCC. Bcl2 is an antiapoptotic protein that regulates chemotherapy in HCC. Metformin is reported to decrease Bcl2 expression, and the purpose of this study was to verify whether metformin could potentiate the anti-HCC efficacy of ATO in vitro. In the present study, we used metformin and ATO alone or in combination and then tested proliferation, apoptosis, and Bcl2 level of HCC cells. The results showed that metformin enhanced both the proliferation-inhibiting and apoptosis-inducing effects of ATO on HCC cell lines HepG2 and BEL7402. Furthermore, this activity proceeded via a mechanism involving metformin-induced downregulation of Bcl2. A combination of ATO and metformin is therefore a potentially promising approach for HCC therapy.

Keywords

Hepatocellular carcinoma Apoptosis Bcl2 Metformin Arsenic trioxide 

Notes

Acknowledgments

The authors appreciate Professor Hanfa Zou and Professor Mingliang Ye for their technical support in the research. This research was supported by the National Nature Science Foundation of China (No. 81272368).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Xuejun Yang
    • 1
    • 2
  • Deguang Sun
    • 2
  • Yu Tian
    • 1
  • Sunbin Ling
    • 2
    • 3
  • Liming Wang
    • 2
  1. 1.Dalian Medical UniversityDalianChina
  2. 2.Department of General SurgeryThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
  3. 3.Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

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