Reduction of anion exchanger 2 expression induces apoptosis of human hepatocellular carcinoma cells

  • Jin-Ming Hwang
  • Shao-Hsuan Kao
  • Yi-Hsien Hsieh
  • Kuen-Lin Li
  • Pei-Hsi Wang
  • Li-Song Hsu
  • Jer-Yuh Liu
Article
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Abstract

Anion exchanger (AE) 2, belonging to the chloride–bicarbonate transporter family, has been reported to involve cell survival for hepatocellular carcinoma (HCC) cells. Our previous findings showed that AE2 gene was highly expressed in a poorly differentiated HCC cell line, HA22T/VGH. Additionally, treatment with 4,4′-diisothiocyanatostilbene-2,20-disulfonic acid (DIDS), an AE-specific inhibitor, significantly inhibited cell proliferation and induced cell apoptosis for the HA22T/VGH. To further investigate the biological functions of AE2 in human HCC, suppression of AE2 expression by the antisense oligonucleotide-AE2 (AS-AE2) was performed, and the cell viability, cell cycle regulation, and cell apoptosis for HCC cell lines were monitored. The results showed that AS-AE2 treatment could efficiently suppress the mRNA expression of AE2 for various differentiated HCC cells, including HA22T/VGH, SK-Hep-1, PLC/PRF/5, Hep3B, and HepG2. Moreover, AS-AE2 treatment significantly reduced cell viability, arrested cell cycle at sub-G1 phase, and induced cell apoptosis for the poorly differentiated HA22T/VGH, but not for other moderately or well-differentiated HCC cell lines. The findings indicated that AE2 may play an important role in the progression of HCC cells, and provide a new strategy for the development of therapeutic treatment against human HCC.

Keywords

Hepatocellular carcinoma Anion exchanger 2 Antisense oligonucleotide 
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Notes

Acknowledgments

This work was supported in part by grants from the National Science Council, Taiwan (NSC 95-2320-B-040-043 and NSC-96-2320-B-040-023-MY2), and from the Chung Shan Medical University, Taiwan (CSMU 96-OM-B-040 and CSMU 93-OM-B-013).

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Jin-Ming Hwang
    • 1
  • Shao-Hsuan Kao
    • 2
  • Yi-Hsien Hsieh
    • 2
  • Kuen-Lin Li
    • 2
  • Pei-Hsi Wang
    • 2
  • Li-Song Hsu
    • 2
  • Jer-Yuh Liu
    • 2
    • 3
  1. 1.Department of Applied Chemistry, School of Medicine, College of MedicineChung Shan Medical UniversityTaichungTaiwan
  2. 2.Institute of Biochemistry and Biotechnology, College of MedicineChung Shan Medical UniversityTaichungTaiwan
  3. 3.Graduate Institute of Cancer BiologyChina Medical UniversityTaichungTaiwan

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