Sensitization of cis-platinum by a recombinant adenovirus vector expressing wild-type p53 gene in human ovarian carcinomas

Oncol Res. 1997;9(11-12):603-9.


Mutations of the tumor suppressor wild-type p53 gene have been implicated in the development of resistance to anticancer drugs. We have examined the role of wild-type p53 in resistance to cis-diamminedichloroplatinum (II) (CDDP) in human ovarian cancer cells using a recombinant adenovirus containing human wild-type p53 cDNA (Adwtp53). In this study we used the human ovarian A2780 tumor cells (wtp53), which are sensitive to CDDP and A2780/CP tumor cells (nonfunctional/mutant p53) and are resistant to CDDP. Studies show that introduction of wtp53 protein via adenovirus gene transfer into A2780/CP cells significantly sensitized these cells to CDDP cytotoxicity, indicating wtp53 was involved in resistance to CDDP. We found that introduction of wtp53 protein also resulted in growth arrest of A2780/CP tumor cells whereas the parent A2780 cells were significantly less sensitive to Adwtp53. This synthesis of wtp53 protein induced by Adwtp53 in A2780/CP cells resulted in a significant increase in the expression of Bax protein without significantly effecting the expression of bcl2 protein, and induced a dose-dependent increase in the nucleosomal DNA fragmentation. The presence of CDDP further enhanced this apoptosis, causing a 30-fold sensitization of A2780/CP cells to CDDP. These results indicate that mutation of p53 protein in A2780/CP ovarian tumor cells resulted in the resistance to CDDP and that combination of wtp53 gene and CDDP may result in sensitization of mutant p53-containing tumors to chemogenetherapy.

MeSH terms

  • Adenoviridae
  • Antineoplastic Agents / therapeutic use*
  • Cell Survival / drug effects
  • Cisplatin / therapeutic use*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • DNA Fragmentation
  • Drug Resistance, Neoplasm / genetics*
  • Enzyme Inhibitors / metabolism
  • Female
  • Genetic Vectors
  • Humans
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics*
  • bcl-2-Associated X Protein


  • Antineoplastic Agents
  • BAX protein, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Cisplatin