Oncolytic adenovirus SG600-IL24 selectively kills hepatocellular carcinoma cell lines.
OBJECTIVE
To investigate the effect of oncolytic adenovirus SG600-IL24 and replication-incompetent adenovirus Ad.IL-24 on hepatocellular carcinoma (HCC) cell lines and normal liver cell line.


METHODS
HCC cell lines (HepG2, Hep3B and MHCC97L) and normal liver cell line (L02) with a different p53 status were infected with SG600-IL24 and Ad.IL-24, respectively. Melanoma differentiation-associated (MDA)-7/interleukin (IL)-24 mRNA and protein expressions in infected cells were detected by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting, respectively. Apoptosis of HCC cells and normal liver cells was detected by cytometric assay with Hoechst33258 staining. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate proliferation of HCC cells and normal liver cells, and cell cycle was assayed by flow cytometry.


RESULTS
RT-PCR, ELISA and Western blotting showed that the exogenous MDA-7/IL-24 gene was highly expressed in cells infected with SG600-IL24. MTT indicated that SG600-IL24 could suppress the growth of HepG2, Hep3B, MHCC97L, with an inhibition rate of 75% ± 2.5%, 85% ± 2.0%, 72% ± 1.8%, respectively (P < 0.01), promote the apoptosis of HepG2, Hep3B, MHCC97L, with an apoptosis rate of 56.59% ± 4.0%, 78.36% ± 3.5%, 43.39% ± 2.5%, respectively (P < 0.01), and block the HCC cell lines in the G2/M phase with a blocking rate of 35.4% ± 4.2%, 47.3% ± 6.2%, 42% ± 5.0%, respectively (P < 0.01) but not the normal liver cell line in a p53-independent manner.


CONCLUSIONS
SG600-IL24 can selectively suppress the proliferation and apoptosis of HCC cell lines in vitro but not normal liver cell line L02 in a p53-independent manner. Compared with Ad.IL-24, SG600-IL24 can significantly enhance the antitumor activity in HCC cell lines.
Xue
Xin-Bo
XB
Department of Biliary and Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
Xiao
Chao-Wen
CW
Zhang
Hui
H
Lu
Ai-Guo
AG
Gao
Wei
W
Zhou
Zhu-Qing
ZQ
Guo
Xin-Lai
XL
Zhong
Ming-An
MA
Yang
Yao
Y
Wang
Cong-Jun
CJ
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D045744:Cell Line, Tumor / Q000821:virology*; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008113:Liver Neoplasms / Q000821:virology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D000099180:Interleukin-24
D007378:Interleukins; D009363:Neoplasm Proteins; D000099180:Interleukin-24