J Korean Med Sci.  1999 Jun;14(3):271-276. 10.3346/jkms.1999.14.3.271.

Adenovirus-mediated p53 tumor suppressor gene therapy against subcutaneous HuH7 hepatoma cell line nodule of nude mice

Affiliations
  • 1Department of Internal Medicine, Kangnam St. Mary's Hospital, College of Medicine, and WHO Collaborating Center for Reference and Research on Viral Hepatitis, The Catholic University of Korea, Seoul.

Abstract

Mutations of the tumor-suppressor gene p53 have been found in 30-50% cases of hepatocellular carcinoma (HCC). In this study, E1-negative adenoviral vector encoding wild-type p53 under the control of the human cytomegalovirus promoter (AdCMV-p53w) was constructed to evaluate its therapeutic efficacy against tumor nodules developing after injection of HuH7 cell lines in ten nude mice. When each nodule had reached 10 mm in perpendicular diameter, 1.5 x 10(8) pfu of AdCMV-p53w per session was injected intratumorally as follows: In group I (n=3), five sessions were injected every other day. In group II (n=3), only one session. Group III (n=4) as negative controls. The mice were sacrificed at 28 days post AdCMV-p53w injection. Tumor growth was significantly suppressed and delayed in group I and II compared to group III as compared by tumor volume at the end of observation. These results suggest that AdCMV-p53w may not only be effective in treating HCCs expressing mutant p53, but also useful as a local injectable gene therapy.

Keyword

Gene, p53; Gene, tumor suppressor; Adenoviridae; Gene therapy; Carcinoma, hepatocellular; HuH7

MeSH Terms

Adenoviruses, Human*
Animal
Apoptosis
Carcinoma, Hepatocellular/therapy*
Carcinoma, Hepatocellular/pathology
Gene Therapy/methods*
Genetic Vectors*
Human
Liver Neoplasms/therapy*
Liver Neoplasms/pathology
Mice
Mice, Nude
Neoplasm Transplantation
Protein p53/genetics*
Tumor Cells, Cultured
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