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Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the Key. | LitMetric

Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the Key.

Int J Mol Sci

Faculty of Biochemistry, Biophysics and Biotechnology, Department of Biophysics and Cancer Biology, Jagiellonian University, 30-387 Krakow, Poland.

Published: July 2023

AI Article Synopsis

  • * The study examines the combined effect of metformin and oxygen microbubbles (OMBs) on breast cancer tumors, focusing on their impact on vasculature, oxygenation, and radiosensitivity.
  • * Results show that using both metformin and OMBs together improved tumor radiosensitivity nearly twofold and normalized abnormal vasculature better than either treatment alone; however, treatment resistance and tumor recurrence remained issues.

Article Abstract

Radiotherapy is a cornerstone of cancer treatment, but tumor hypoxia and resistance to radiation remain significant challenges. Vascular normalization has emerged as a strategy to improve oxygenation and enhance therapeutic outcomes. In this study, we examine the radiosensitization potential of vascular normalization using metformin, a widely used anti-diabetic drug, and oxygen microbubbles (OMBs). We investigated the synergistic action of metformin and OMBs and the impact of this therapeutic combination on the vasculature, oxygenation, invasiveness, and radiosensitivity of murine 4T1 breast cancer. We employed in vivo Doppler ultrasonographic imaging for vasculature analysis, electron paramagnetic resonance oximetry, and immunohistochemical assessment of microvessels, perfusion, and invasiveness markers. Our findings demonstrate that both two-week metformin therapy and oxygen microbubble treatment normalize abnormal cancer vasculature. The combination of metformin and OMB yielded more pronounced and sustained effects than either treatment alone. The investigated therapy protocols led to nearly twice the radiosensitivity of 4T1 tumors; however, no significant differences in radiosensitivity were observed between the various treatment groups. Despite these improvements, resistance to treatment inevitably emerged, leading to the recurrence of hypoxia and an increased incidence of metastasis.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418665PMC
http://dx.doi.org/10.3390/ijms241512156DOI Listing

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