Efficacy of tumor-targeting Salmonella typhimurium A1-R on nude mouse models of metastatic and disseminated human ovarian cancer

J Cell Biochem. 2014 Nov;115(11):1996-2003. doi: 10.1002/jcb.24871.

Abstract

We report here the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on mouse models of disseminated and metastatic ovarian cancer. The proliferation-inhibitory efficacy of A1-R on human ovarian cancer cell lines (SKOV-3-GFP, OVCAR-3-RFP) was initially demonstrated in vitro. Orthotopic and dissemination mouse models of ovarian cancer were made with the human ovarian cancer cell line SKOV-3-GFP. After tumor implantation, the mice were treated with A1-R (5 × 10(7) colony-forming units [CFU], i.v.), and there were no severe adverse events observed. In the orthotopic model, tumor volume after treatment was 276 ± 60.8 mm(3), compared to 930 ± 342 mm(3) in the untreated control group (P = 0.022). There was also a significant difference in survival between treated mice and untreated mice in a peritoneal dissemination model (P = 0.005). The results of this report demonstrate that A1-R is effective for highly aggressive human ovarian cancer in metastatic and dissemination mouse models and suggest its clinical potential for this highly treatment-resistant disease.

Keywords: BACTERIA; GFP; IMAGING; NUDE MICE; OVARIAN CANCER; Salmonella typhimurium; TUMOR-TARGETING.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy*
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / secondary*
  • Peritoneal Neoplasms / therapy*
  • Salmonella Infections / pathology*
  • Salmonella typhimurium / classification
  • Salmonella typhimurium / pathogenicity*
  • Survival Analysis
  • Xenograft Model Antitumor Assays