Enhanced therapeutic effect of cisplatin on the prostate cancer in tumor-bearing mice by transfecting the attenuated Salmonella carrying a plasmid co-expressing p53 gene and mdm2 siRNA

Cancer Lett. 2013 Aug 28;337(1):133-42. doi: 10.1016/j.canlet.2013.05.028. Epub 2013 May 29.

Abstract

Prostate cancer urgently needs an efficient therapy. Here we demonstrated that cisplatin combined with gene therapy by transfecting the attenuated Salmonella that carry a plasmid containing p53 gene and MDM2 siRNA provided a super-synergistic effect on the inhibition of prostate cancer growth in vivo. This synergistic therapy was associated with the induction of apoptotic cell death with a decreased Bcl2 to Bax expression ratio and increased expression of cleaved caspase 3 and caspase 9 in the prostate cancer xenograft. These results indicate that cisplatin-chemotherapy in combination with targeting the MDM2/p53 axis is an attractive strategy to treat prostate cancer.

Keywords: Apoptosis; Cisplatin (DDP); P53; Prostate cancer; Si RNA-mdm2; Xenograft mice model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cisplatin / therapeutic use*
  • Combined Modality Therapy
  • Genes, p53*
  • Genetic Therapy*
  • Humans
  • Male
  • Mice
  • Prostatic Neoplasms / therapy*
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • RNA, Small Interfering / genetics*
  • Salmonella typhimurium / genetics

Substances

  • Antineoplastic Agents
  • RNA, Small Interfering
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Cisplatin