The growth inhibitory effect of p21 adenovirus on androgen-dependent and -independent human prostate cancer cells

BJU Int. 2003 Aug;92(3):314-8. doi: 10.1046/j.1464-410x.2003.04318.x.

Abstract

Objective: To assess the potential of p21 as a gene therapy treatment for prostate cancer, by introducing p21 into both androgen-dependent (AD) and -independent (AI) human prostate cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p21, carrying human p21 cDNA.

Materials and methods: The LNCaP, DU145 and PC-3 human prostate cancer cell lines were cultured and infected with Ad5CMV-p21. Cell growth, cell-cycle progression and tumorigenicity were then assessed by thymidine incorporation into cellular DNA, and cell number, flow cytometry, and tumour growth after inoculating the cells into nude mice.

Results: Growth was inhibited in Ad5CMV-p21 viral-infected AD and AI prostate cancer cells. The effects were dose-dependent, regardless of the androgen status of the cell lines. Flow cytometric analysis showed that Ad5CMV-p21 arrested cell-cycle progression at G1/S with no appreciable effect on the levels of apoptotic cells. The tumorigenicity of cancer cells infected with Ad5CMV-p21 was greatly reduced in athymic mice.

Conclusions: These results suggest that Ad5CMV-p21 may be a new therapeutic agent for human prostate cancer gene therapy.

MeSH terms

  • Adenoviridae*
  • Androgens
  • Cell Division
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / administration & dosage
  • Cyclins / genetics*
  • Flow Cytometry
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Male
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Tumor Cells, Cultured

Substances

  • Androgens
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins