Antiglycolytic Therapy Combined with an Image-guided Minimally Invasive Delivery Strategy for the Treatment of Breast Cancer

Abstract

Purpose: The antiglycolytic agent 3-bromopyruvate (3-BrPA) promotes anticancer effects in multiple Minor 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.