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

Manon Buijs, Joost W. Wijlemans, Byung Kook Kwak, Shinichi Ota, Jean Francois H. Geschwind

Research output: Contribution to journalArticlepeer-review

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 mm3±346 and 426 mm3±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.

Original languageEnglish (US)
Pages (from-to)737-743
Number of pages7
JournalJournal of Vascular and Interventional Radiology
Volume24
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • 3-BrPA
  • 3-bromopyruvate
  • ATP
  • GAPDH
  • H&E
  • MEM
  • MMP
  • PBS
  • PCR
  • adenosine triphosphate
  • glyceraldehyde 3-phosphate dehydrogenase
  • hematoxylin and eosin
  • matrix metalloproteinase
  • modified Eagle medium
  • phosphate-buffered saline
  • polymerase chain reaction

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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