Synergistic chemosensitization and inhibition of tumor growth and metastasis by adenovirus-mediated P53 gene transfer in human bladder cancer model

Urology. 2000 Aug 1;56(2):332-6. doi: 10.1016/s0090-4295(00)00567-7.


Objectives: To determine whether an adenovirus-mediated p53 gene (Ad5CMV-p53) transfer enhances cisplatin cytotoxicity in vitro and whether Ad5CMV-p53 and cisplatin synergistically inhibit growth and metastasis in vivo using human bladder cancer KoTCC-1 cells.

Methods: MTT assays and DNA fragmentation assays were used to examine the effects of treatment with Ad5CMV-p53 and/or cisplatin on growth inhibition and induction of apoptosis, respectively, in KoTCC-1 cells. The efficacies of combined Ad5CMV-p53 and/or cisplatin therapy against growth and metastasis of KoTCC-1 tumors were assessed using subcutaneous and orthotopic tumor cell injection models.

Results: Ad5CMV-p53 substantially enhanced cisplatin chemosensitivity in a dose-dependent manner, reducing the median IC(50) by more than 50%. Characteristic apoptotic DNA laddering was induced by the combination of sublethal doses of Ad5CMV-p53 and cisplatin, but not by either agent alone. Furthermore, combined Ad5CMV-p53 and cisplatin therapy synergistically inhibited growth of subcutaneous KoTCC-1 tumors and the incidence of metastasis after orthotopic injection.

Conclusions: These findings illustrate that combined treatment with Ad5CMV-p53 and cisplatin could be an attractive strategy for inhibiting progression of bladder cancer through effective induction of apoptosis.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use*
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm
  • Female
  • Gene Transfer Techniques
  • Genes, p53*
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*


  • Antineoplastic Agents
  • Cisplatin