Mechanism of the combination effect of wild-type TP53 gene transfection and cisplatin treatment for ovarian cancer xenografts

Eur J Cancer. 2000 Sep;36(14):1869-75. doi: 10.1016/s0959-8049(00)00161-1.

Abstract

To clarify the effect of a combination treatment consisting of a recombinant adenovirus carrying a wild-type TP53 gene (AxCATP53) and cisplatin (CDDP), we examined p53-dependent apoptosis in ovarian cancer xenografts with and without the wild-type TP53 gene. Severe combined immunodeficiency (SCID) mice were implanted with ovarian cancer cell lines consisting of SK-OV-3 cells without the TP53 gene and KF cells with the TP53 gene. In SK-OV-3 and KF tumours, the inhibitory effect of the combination treatment on tumour growth was significant, compared with a single treatment with CDDP alone or AxCATP53 alone. The apoptotic index increased significantly after combination treatment in the SK-OV-3 tumours. The expression of Bax protein in SK-OV-3 tumours was weak, but strengthened after TP53 gene transfection. In contrast, AxCATP53 transfection did not affect CDDP-induced apoptosis in the KF tumours. Therefore, combination treatment of AxCATP53 and CDDP may be a new strategy for treating ovarian cancer with or without the TP53 gene.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cisplatin / therapeutic use*
  • Female
  • Genes, p53 / genetics*
  • Humans
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / therapy*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2*
  • Transfection / methods*
  • Transformation, Genetic*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • Bax protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Cisplatin