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-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.
Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Chao-Wen
CW
Xiao
Xin-Bo
XB
Xue
Hui
H
Zhang
Wei
W
Gao
Yuan
Y
Yu
Kun
K
Chen
Jian-Wei
JW
Zheng
Cong-Jun
CJ
Wang
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D002453:Cell Cycle / Q000502:physiology; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D000099180:Interleukin-24
D007378:Interleukins; D000099180:Interleukin-24