Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R inhibits disseminated human ovarian cancer and extends survival in nude mice

Yasunori Matsumoto, Shinji Miwa, Yong Zhang, Ming Zhao, Shuya Yano, Fuminari Uehara, Mako Yamamoto, Yukihiko Hiroshima, Makoto Toneri, Michael Bouvet, Hisahiro Matsubara, Hiroyuki Tsuchiya, Robert M. Hoffman

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42 Citations (Scopus)

Abstract

Peritoneal disseminated cancer is highly treatment resistant. We here report the efficacy of intraperitoneal (i.p.) administration of tumor-targeting Salmonella typhimurium A1-R in a nude mouse model of disseminated human ovarian cancer. The mouse model was established by intraperitoneal injection of the human ovarian cancer cell line SKOV3-GFP. Seven days after implantation, mice were treated with S. typhimurium A1-R via intravenous (i.v.) or i.p. administration at the same dose, 5×107 CFU, once per week. Both i.v. and i.p. treatments effected prolonged survival compared with the untreated control group (P=0.025 and P<0.001, respectively). However, i.p. treatment was less toxic than i.v. treatment. Tumor-specific targeting of S. typhimurium A1-R was confirmed with bacterial culture from tumors and various organs and tumor or organ colony formation after i.v. or i.p. injection. Selective tumor targeting was most effective with i.p. administration. The results of the present study show S. typhimurium A1-R has promising clinical potential for disseminated ovarian cancer, especially via i.p. administration.

Original languageEnglish
Pages (from-to)11369-11377
Number of pages9
JournalOncotarget
Volume6
Issue number13
DOIs
Publication statusPublished - 2015

Keywords

  • Bacterial therapy
  • Mouse model
  • Orthotopic
  • Ovarian cancer
  • Salmonella typhimurium A1-R

ASJC Scopus subject areas

  • Oncology

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    Matsumoto, Y., Miwa, S., Zhang, Y., Zhao, M., Yano, S., Uehara, F., Yamamoto, M., Hiroshima, Y., Toneri, M., Bouvet, M., Matsubara, H., Tsuchiya, H., & Hoffman, R. M. (2015). Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R inhibits disseminated human ovarian cancer and extends survival in nude mice. Oncotarget, 6(13), 11369-11377. https://doi.org/10.18632/oncotarget.3607