[Anti-tumor effect of E1B55kDa-deleted adenovirus on human hepatocellular carcinoma cell lines].
OBJECTIVE
To investigate the in vitro and in vivo anti-tumoral effect of E1B55kDa-deleted adenovirus (dl1520) on human hepatocellular carcinoma (HCC) cell lines.


METHODS
Human HCC cell lines with different p53 genotypes were infected with dl1520. Four days after infection, the percentage of survival cells was determined by colorimetric assay. RT-polymerase chain reaction (PCR) was used to examine alterations of p53 and p21Waf-1 expression. Adenovirus hexon gene expression was applied to prove the presence of adenovirus infections. Effects on vivo anti-tumor dl1520 were examined with intra-tumor injection of dl1520 in the SCID mice.


RESULTS
After the infection, the p53-null HCC cell line, Hep3B was most vulnerable to dl1520 induced cytotoxic effect with a cell death rate of more than 60%. Whereas, less than 20% PLC/PRF/5 (p53-mutant) and HepG2 (p53-wild type) HCC cell lines were killed. The expression of p53 and p21Waf-1 was considerably enhanced after the dl1520 infection in HepG2. The intra-tumor injection of dl1520 significantly reduced the tumor growth in Hep3B xenografts. In contrast, no obvious tumor repression was observed in HepG2 and PLC/PRF/5 xenografts.


CONCLUSIONS
dl1520 selectively kills the p53-null hepatocellular carcinoma, showing potential application for cancer treatment.
Zhao
J
J
Cancer Research Institute, Second Military Medical University, Shanghai 200433, China.
Lü
Y
Y
Guo
Y
Y
D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000502:physiology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D017501:Adenovirus E1B Proteins; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53