TY - JOUR
T1 - Antiglycolytic therapy combined with an image-guided minimally invasive delivery strategy for the treatment of breast cancer
AU - Buijs, Manon
AU - Wijlemans, Joost W.
AU - Kwak, Byung Kook
AU - Ota, Shinichi
AU - Geschwind, Jean Francois H.
N1 - Funding Information:
This work was supported by National Institutes of Health T32 Grant 5T32EB006351-05 (to M.B.). J.F.H.G. is the founder of Prescience Labs (Baltimore, Maryland), which is developing 3-bromopyruvate for clinical use in liver cancer. None of the other authors have identified a conflict of interest.
Funding Information:
This work was supported by the Abdulrahman Abdulmalik Research Fund and Charles Wallace Pratt Research Fund. The authors acknowledge the contributions of Dr. Mustafa Vali, who died unexpectedly when the manuscript was under preparation. Dr. Vali was a great source of inspiration to us and will be greatly missed.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/5
Y1 - 2013/5
N2 - 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.
AB - 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.
KW - 3-BrPA
KW - 3-bromopyruvate
KW - ATP
KW - GAPDH
KW - H&E
KW - MEM
KW - MMP
KW - PBS
KW - PCR
KW - adenosine triphosphate
KW - glyceraldehyde 3-phosphate dehydrogenase
KW - hematoxylin and eosin
KW - matrix metalloproteinase
KW - modified Eagle medium
KW - phosphate-buffered saline
KW - polymerase chain reaction
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U2 - 10.1016/j.jvir.2013.01.013
DO - 10.1016/j.jvir.2013.01.013
M3 - Article
C2 - 23489770
AN - SCOPUS:84876924193
SN - 1051-0443
VL - 24
SP - 737
EP - 743
JO - Journal of Vascular and Interventional Radiology
JF - Journal of Vascular and Interventional Radiology
IS - 5
ER -