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

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 vasc...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-08, Vol.24 (15), p.12156
Main Authors: Drzał, Agnieszka, Dziurman, Gabriela, Hoła, Paweł, Lechowski, Jakub, Delalande, Anthony, Swakoń, Jan, Pichon, Chantal, Elas, Martyna
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Antidiabetics
Blood vessels
Brain cancer
Breast cancer
Cancer therapies
Health aspects
Homeopathy
Hypoxia
Life Sciences
Lungs
Materia medica and therapeutics
Metastasis
Metformin
oxygen microbubbles
Radiation therapy
radiotherapy
Respiration
Therapeutics
Tumors
Type 2 diabetes
Ultrasonic imaging
Vascular endothelial growth factor
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241512156