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Updated: Apr 1, 2026
Pre-clinical Orthotopic Murine Model of Human Prostate Cancer
Published on: August 29, 2016
Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse
Makoto Toneri1,2,3, Shinji Miwa1,2, Yong Zhang1
1AntiCancer Inc., San Diego, California, USA.
Abstract:
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.
Insights
Salmonella typhimurium A1-R effectively inhibits prostate cancer bone metastasis. This tumor-targeting therapy, alone or with zoledronic acid, shows promise for improving patient survival and clinical outcomes.
Area of Science:
- Oncology
- Microbiology
- Cancer Metastasis Research
Background:
- Bone metastasis is a common and lethal complication of prostate cancer.
- Current treatments like zoledronic acid (ZOL) have limited efficacy.
- Novel therapeutic strategies are needed to improve outcomes for prostate cancer patients with bone metastasis.
Purpose of the Study:
- To evaluate the efficacy of tumor-targeting Salmonella typhimurium A1-R against prostate cancer bone metastasis.
- To compare the effects of S. typhimurium A1-R, ZOL, and combination therapy in preclinical models.
Main Methods:
- In vitro analysis of S. typhimurium A1-R and ZOL on prostate cancer cell growth.
- Establishment of early and advanced stage experimental bone metastasis mouse models.
- In vivo treatment with ZOL, S. typhimurium A1-R, and combination therapy.
Main Results:
- Both ZOL and S. typhimurium A1-R inhibited prostate cancer cell growth in vitro.
- S. typhimurium A1-R significantly reduced bone metastasis and delayed its appearance in mouse models.
- Combination therapy showed synergistic effects, improving overall survival in mice with multiple bone metastases.
Conclusions:
- S. typhimurium A1-R demonstrates significant potential in preventing and inhibiting prostate cancer bone metastasis.
- This therapy warrants further investigation for clinical application as an adjuvant treatment.
