Efficacy of tumor-targeting Salmonella typhimurium A1-R in combination with anti-angiogenesis therapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) and cellline mouse models

Yukihiko Hiroshima, Yong Zhang, Takashi Murakami, Ali Maawy, Shinji Miwa, Mako Yamamoto, Shuya Yano, Sho Sato, Masashi Momiyama, Ryutaro Mori, Ryusei Matsuyama, Takashi Chishima, Kuniya Tanaka, Yasushi Ichikawa, Michael Bouvet, Itaru Endo, Ming Zhao, Robert M. Hoffman

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Abstract

The aim of the present study was to examine the efficacy of tumor-targeting Salmonella typhimurium A1-R treatment following anti-vascular endothelial growth factor (VEGF) therapy on VEGF-positive human pancreatic cancer. A pancreatic cancer patient-derived orthotopic xenograft (PDOX) that was VEGF-positive and an orthotopic VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) as well as a VEGFnegative cell line (Panc-1) were tested. Nude mice with these tumors were treated with gemcitabine (GEM), bevacizumab (BEV), and S. typhimurium A1-R. BEV/GEM followed by S. typhimurium A1-R significantly reduced tumor weight compared to BEV/GEM treatment alone in the PDOX and MiaPaCa-2 models. Neither treatment was as effective in the VEGF-negative model as in the VEGF-positive models. These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the PDOX model, suggesting its clinical potential.

Original languageEnglish
Pages (from-to)12346-12357
Number of pages12
JournalOncotarget
Volume5
Issue number23
DOIs
Publication statusPublished - Jan 1 2014

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Keywords

  • Anti-angiogenic therapy
  • Bevacizumab
  • GFP
  • Gemcitabine
  • Nude mice
  • Orthotopic
  • Pancreatic cancer
  • Patient-derived orthotopic xenograft (PDOX)
  • Salmonella typhimurium A1-R
  • VEGF

ASJC Scopus subject areas

  • Oncology

Cite this

Hiroshima, Y., Zhang, Y., Murakami, T., Maawy, A., Miwa, S., Yamamoto, M., Yano, S., Sato, S., Momiyama, M., Mori, R., Matsuyama, R., Chishima, T., Tanaka, K., Ichikawa, Y., Bouvet, M., Endo, I., Zhao, M., & Hoffman, R. M. (2014). Efficacy of tumor-targeting Salmonella typhimurium A1-R in combination with anti-angiogenesis therapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) and cellline mouse models. Oncotarget, 5(23), 12346-12357. https://doi.org/10.18632/oncotarget.2641