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J Vasc Interv Radiol. 2013 May;24(5):737-43. doi: 10.1016/j.jvir.2013.01.013. Epub 2013 Mar 13.

Antiglycolytic therapy combined with an image-guided minimally invasive delivery strategy for the treatment of breast cancer.

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1
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Abstract

PURPOSE:

The antiglycolytic agent 3-bromopyruvate (3-BrPA) promotes anticancer effects in multiple tumor models. This study evaluated the therapeutic efficacy of ultrasound (US)-guided intratumoral delivery of 3-BrPA in an orthotopic tumor model of breast cancer.

MATERIALS AND METHODS:

Human breast cancer cell line MDA MB 231 was used for in vitro and in vivo studies. The anticancer effect of 3-BrPA was evaluated by viability assay, quantification of adenosine triphosphate (ATP) and lactate levels, and activity of matrix metalloproteinase (MMP)-9. In animal experiments, 15 nude mice with MDA MB 231 breast tumors were divided into three groups for US-guided intratumoral treatment with 1.75 mM 3-BrPA (group 1), 5 mM 3-BrPA (group 2), and saline solution (group 3). Tumor size was measured and subjected to histopathologic examination.

RESULTS:

In vitro, treatment with 3-BrPA resulted in a dose-dependent decrease in cell viability. A decrease in ATP and lactate levels, invasion, and MMP9 activity and expression was observed after treatment with concentrations of 3-BrPA that did not affect cell viability. In vivo, a significant difference in tumor volume was observed between 3-BrPA-treated and control animals. At the end of the study, tumor volumes in the 3-BrPA groups were 1,876 mm(3)±346 and 426 mm(3)±180 in the 1.75-mM and 5-mM 3-BrPA groups, respectively, versus 4,447 mm(3)±571 in the control group (P< .05).

CONCLUSIONS:

US-guided intratumoral injection of 3-BrPA effectively blocks breast cancer progression in an orthotopic mouse tumor model.

PMID:
23489770
DOI:
10.1016/j.jvir.2013.01.013
[Indexed for MEDLINE]
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