Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models
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Makoto Toneri1,2,3, Shinji Miwa1,2, Yong Zhang1, Cameron Hu1, Shuya Yano1,2, Yasunori Matsumoto2, Michael Bouvet2, Hayao Nakanishi4, Robert M. Hoffman1,2 and Ming Zhao1
1 AntiCancer, Inc., San Diego, California, USA
2 Department of Surgery, University of California, San Diego, California, USA
3 Ageo Medical Group, Saitama, Japan
4 Laboratory of Pathology and Clinical Research, Aichi Cancer Center Aichi Hospital, Aichi, Japan
Ming Zhao, email:
Robert M. Hoffman, email:
Keywords: prostate cancer, bone metastasis, GFP/RFP, zoledronic acid, bacterial therapy
Received: July 20, 2015 Accepted: August 14, 2015 Published: September 28, 2015
Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting.
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