Oncolytic adenovirus-mediated MDA-7/IL-24 overexpression enhances antitumor activity in hepatocellular carcinoma cell lines

BACKGROUND:Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24(IL-24)is a novel tumor suppressor gene,which has suppressor activity in a broad spectrum of human cancer cells.We investigated the effect of the replication-competent oncolytic adenovirus SG600-IL24 and replication-incompet...

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Published in:Hepatobiliary & pancreatic diseases international 2010-12, Vol.9 (6), p.615-621
Main Authors: Xiao, Chao-Wen, Xue, Xin-Bo, Zhang, Hui, Gao, Wei, Yu, Yuan, Chen, Kun, Zheng, Jian-Wei, Wang, Cong-Jun
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
adenovirus
Apoptosis - physiology
carcinoma
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - therapy
Cell Cycle - physiology
differentiation-associated
Flow Cytometry
gene
Gene Expression - physiology
gene-7
Genetic Therapy - methods
Hep G2 Cells
hepatocellular
Hepatocytes - cytology
Hepatocytes - physiology
Humans
interleukin-24
Interleukins - genetics
Interleukins - metabolism
Liver Neoplasms - genetics
Liver Neoplasms - therapy
melanoma
oncolytic
therapy
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Summary:BACKGROUND:Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24(IL-24)is a novel tumor suppressor gene,which has suppressor activity in a broad spectrum of human cancer cells.We investigated the effect of the replication-competent oncolytic adenovirus SG600-IL24 and replication-incompetent adenovirus Ad.IL-24,both expressing human MDA-7/IL-24 on the hepatocellular carcinoma cell lines HepG2,Hep3B,SMMC-7721,HCCLM3,and the normal liver cell line L02. METHODS:Hepatocellular carcinoma cell lines and the normal liver cell line were infected with SG600-IL24 and Ad.IL-24.The mRNA and protein expression of MDA-7/IL-24 in infected cells was confirmed by RT-PCR,ELISA,and Western blotting.MTT assay was used to investigate the proliferation effect.Hoechst staining and Annexin-V and PI staining were performed to study the MDA-7/IL-24 gene expressed in HCC cell lines and the normal liver cell line.Flow cytometry was used to analyse the cell cycle. RESULTS:RT-PCR,ELISA and Western blotting confirmed that the exogenous MDA-7/IL-24 gene was highly expressed in cells infected with SG600-IL24.MTT and apoptosis detection indicated that SG600-IL24 induced growth suppression promoted apoptosis,and blocked cancer cell lines in the G2/M phase in hepatocellular carcinoma cell lines but not in the normal liver cell line. CONCLUSIONS:SG600-IL24 selectively induces growth suppression and apoptosis in hepatocellular carcinoma cell lines in vitro but not in the normal liver cell line L02. Compared with Ad.IL-24,SG600-IL24 dramatically enhances antitumor activity in hepatocellular carcinoma cell lines.
ISSN:1499-3872