Reduction of anion exchanger 2 expression induces apoptosis of human hepatocellular carcinoma cells.
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.
Hwang
Jin-Ming
JM
Department of Applied Chemistry, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
Kao
Shao-Hsuan
SH
Hsieh
Yi-Hsien
YH
Li
Kuen-Lin
KL
Wang
Pei-Hsi
PH
Hsu
Li-Song
LS
Liu
Jer-Yuh
JY
D027321:Anion Transport Proteins / Q000235:genetics* / Q000378:metabolism; D017920:Antiporters / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D064606:SLC4A Proteins
D027321:Anion Transport Proteins; D017920:Antiporters; D012333:RNA, Messenger; D064606:SLC4A Proteins