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.
Conclusion: dl1520 selectively kills the p53-null hepatocellular carcinoma, showing potential application for cancer treatment.