Oncotarget

Research Papers:

Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model

Keshab Raj Parajuli, Qiuyang Zhang, Sen Liu and Zongbing You _

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Oncotarget. 2016; 7:10616-10626. https://doi.org/10.18632/oncotarget.7055

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Abstract

Keshab Raj Parajuli1, Qiuyang Zhang1, Sen Liu1, Zongbing You1,2,3,4,5

1Departments of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana 70112, USA

2Department of Orthopaedic Surgery, Tulane University, New Orleans, Louisiana 70112, USA

3Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane University, New Orleans, Louisiana 70112, USA

4Tulane Center for Stem Cell Research and Regenerative Medicine, Tulane University, New Orleans, Louisiana 70112, USA

5Tulane Center for Aging, Tulane University, New Orleans, Louisiana 70112, USA

Correspondence to:

Zongbing You, e-mail: zyou@tulane.edu

Keywords: aminomethylphosphonic acid, glyphosate, prostate cancer, metastasis, orthotopic xenograft mouse model

Received: October 01, 2015    Accepted: January 23, 2016    Published: January 28, 2016

ABSTRACT

Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer.


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