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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/12156 |
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| author | Agnieszka Drzał Gabriela Dziurman Paweł Hoła Jakub Lechowski Anthony Delalande Jan Swakoń Chantal Pichon Martyna Elas |
| author_facet | Agnieszka Drzał Gabriela Dziurman Paweł Hoła Jakub Lechowski Anthony Delalande Jan Swakoń Chantal Pichon Martyna Elas |
| author_sort | Agnieszka Drzał |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T00:25:02Z |
| format | Article |
| id | doaj.art-08da7a40992b4fb9bed96d31cea72197 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:25:02Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-08da7a40992b4fb9bed96d31cea721972023-11-18T23:01:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151215610.3390/ijms241512156Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the KeyAgnieszka Drzał0Gabriela Dziurman1Paweł Hoła2Jakub Lechowski3Anthony Delalande4Jan Swakoń5Chantal Pichon6Martyna Elas7Faculty of Biochemistry, Biophysics and Biotechnology, Department of Biophysics and Cancer Biology, Jagiellonian University, 30-387 Krakow, PolandFaculty of Biochemistry, Biophysics and Biotechnology, Department of Biophysics and Cancer Biology, Jagiellonian University, 30-387 Krakow, PolandFaculty of Biochemistry, Biophysics and Biotechnology, Department of Biophysics and Cancer Biology, Jagiellonian University, 30-387 Krakow, PolandFaculty of Biochemistry, Biophysics and Biotechnology, Department of Biophysics and Cancer Biology, Jagiellonian University, 30-387 Krakow, PolandUFR Sciences and Techniques, University of Orleans, 45067 Orleans, FranceInstitute of Nuclear Physics, Polish Academy of Sciences, 31-342 Krakow, PolandUFR Sciences and Techniques, University of Orleans, 45067 Orleans, FranceFaculty of Biochemistry, Biophysics and Biotechnology, Department of Biophysics and Cancer Biology, Jagiellonian University, 30-387 Krakow, PolandRadiotherapy 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.https://www.mdpi.com/1422-0067/24/15/12156oxygen microbubblesmetforminhypoxiaradiotherapybreast cancer |
| spellingShingle | Agnieszka Drzał Gabriela Dziurman Paweł Hoła Jakub Lechowski Anthony Delalande Jan Swakoń Chantal Pichon Martyna Elas Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the Key International Journal of Molecular Sciences oxygen microbubbles metformin hypoxia radiotherapy breast cancer |
| title | Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the Key |
| title_full | Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the Key |
| title_fullStr | Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the Key |
| title_full_unstemmed | Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the Key |
| title_short | Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the Key |
| title_sort | murine breast cancer radiosensitization using oxygen microbubbles and metformin vessels are the key |
| topic | oxygen microbubbles metformin hypoxia radiotherapy breast cancer |
| url | https://www.mdpi.com/1422-0067/24/15/12156 |
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