Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R inhibits disseminated human ovarian cancer and extends survival in nude mice
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Yasunori Matsumoto1,2,3,*, Shinji Miwa1,2,4,*, Yong Zhang1, Ming Zhao1, Shuya Yano1,2, Fuminari Uehara1,2, Mako Yamamoto1,2, Yukihiko Hiroshima1,2, Makoto Toneri1,2, Michael Bouvet2, Hisahiro Matsubara3, Hiroyuki Tsuchiya4 and Robert M. Hoffman1,2
1 AntiCancer, Inc, San Diego, CA, USA
2 Department of Surgery, University of California San Diego, San Diego, CA, USA
3 Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
4 Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan
* These authors contributed equally to this work
Robert M. Hoffman, email:
Ming Zhao, email:
Keywords: ovarian cancer, orthotopic, mouse model, bacterial therapy, Salmonella typhimurium A1-R
Received: February 06, 2015 Accepted: February 21, 2015 Published: March 16, 2015
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.
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