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The cytotoxic effect of E1B 55-kDa mutant adenovirus on human hepatocellular carcinoma cell lines

Cancer Gene Therapy volume 8, pages 333–341 (2001)Cite this article

Abstract

It has been suggested the E1B 55 kDa mutant adenovirus dl1520 can selectively killp53-deficient human tumor cells. In this study, we examined the cytotoxic effect of dl1520 on nine human hepatocellular carcinoma (HCC) cell lines with differentp53 genetic and functional status. The results showed that HCC cell lines with deleted or mutantp53 gene and reducedp53 transcriptional activities were more susceptible to dl1520-induced cytolysis. Hep3B (p53-null) and HepG2 (p53-wt) cells were arrested at G2/M phase when cytolysis occurred. Cyclin-dependent kinase inhibitor (CDKI) p21Waf-1/Cip-1 was downregulated 24 hours after dl1520 infection in HepG2 cells and increased when cytolysis occurred. No p21 expression was detected in Hep3B cells. DNA fragmentation was found in both Hep3B and HepG2 cells after dl1520 infection. Bax expression increased in dl1520-infected HepG2 cells but not in Hep3B cells. Notably, three Bax-like proteins, molecular mass around 40 to 80 kDa, accumulated 48 hours after adenovirus infection in Hep3B cells but not in HepG2 cells. These results suggest that the susceptibility of HCC cells to dl1520-induced cytolysis is related to bothp53 genotype and functional status, and is mediated by both cell cycle disturbance and apoptosis. Cancer Gene Therapy (2001) 8, 333–341

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Acknowledgements

This work is supported by grants from National Natural Science Foundation (NNSF) of China, the Shanghai Commission of Science and Technology, Shanghai Bureau of Public Health and The State Commission of Education of People's Republic of China to Y. J. Guo, J. Zhao and L. X. Wei. We specially thank the Commission of Science and Technology of Shanghai Pu-Dong New District for the strong financial support through a New District Key Grant. We thank Berk A. J. (Los Angles, CA) for kindly providing adenovirus dl1520 and Dr. Miltry R. (London, UK) for generous help in this study.

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Authors and Affiliations

  1. International Cancer Institute and Eastern Hospital of Hepatobiliary Surgery, the Second Military Medical University, Shanghai, 200433, People's Republic of China

    Jian Zhao, Hao Wang, Lixing Wei & Yajun Guo

  2. Shanghai Bio-Technology Center, Pu Dong High-Tech District, Shanghai, People's Republic of China

    Jian Zhao, Hao Wang, Lixing Wei, Mengchao Wu & Yajun Guo

  3. Department of Surgery, Imperial College School of Medicine, Hammersmith Hospital Campus, Du Cane Road, London, W12 ONN, UK

    Nagy A Habib

  4. Ludwig Institute for Cancer Research, Imperial College School of Medicine, St. Mary's Hospital Campus, Norfolk Place, London, W2 1PG, UK

    Xin Lu

  5. Eppley Cancer Institute and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68198-6805, Nebraska

    Yajun Guo

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Correspondence to Yajun Guo.

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Zhao, J., Wang, H., Wei, L. et al. The cytotoxic effect of E1B 55-kDa mutant adenovirus on human hepatocellular carcinoma cell lines. Cancer Gene Ther 8, 333–341 (2001). https://doi.org/10.1038/sj.cgt.7700316

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