Related Experiment Video
Updated: Jul 22, 2025
Live Imaging of Microtubule Dynamics in Glioblastoma Cells Invading the Zebrafish Brain
Published on: July 29, 2022
Azithromycin inhibits glioblastoma angiogenesis in mice via inducing mitochondrial dysfunction and oxidative stress
Xiulan Zhang1,2, Haibo Xu3
1Department of Radiology, Zhongnan Hospital of Wuhan University, 160 Donghu Road, 430071, Wuhan, People's Republic of China.
Abstract:
The poor outcomes in glioblastoma (GBM) necessitate new treatments. As GBM is highly vascularized and its growth is largely dependent on angiogenesis, angiogenesis inhibitors have been hotly evaluated in clinical trials for GBM treatment for the last decade. In line with these efforts, our work reveals that azithromycin, a clinically available antibiotic, is a novel angiogenesis inhibitor. Azithromycin inhibits vessel structure formation on Matrigel of GBM-derived endothelial cell (ECs) and other types of ECs. Time course analysis shows that azithromycin interferes with the early stage of angiogenesis. Azithromycin also inhibits GBM-derived EC adhesion, growth and survival but not migration. The transgenic zebrafish Tg (fli1a: EGFP) model clearly shows that azithromycin inhibits angiogenesis in vivo. Of note, azithromycin at non-toxic dose inhibits GBM growth in mice and increases overall survival, and furthermore, this is associated with angiogenesis inhibition. Mechanism studies show that azithromycin decreases mitochondrial respiration by suppressing the activity of multiple complexes, leading to ATP reduction, oxidative stress and damage. In addition, oxidative stress induced by azithromycin is through thiol redox-mediated pathways. Our work demonstrates the anti-angiogenic activity of azithromycin via inducing mitochondrial dysfunction and oxidative stress. Our pre-clinical evidence provides a rationale for initiating clinical trials using azithromycin in combination with standard-of-care drugs for GBM patients.
Insights
Azithromycin, an antibiotic, inhibits glioblastoma growth by blocking angiogenesis, the formation of new blood vessels. This novel finding suggests azithromycin as a potential treatment for glioblastoma (GBM) patients.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Glioblastoma (GBM) has poor patient outcomes, necessitating novel therapeutic strategies.
- Angiogenesis is crucial for GBM growth, making angiogenesis inhibitors a key research area.
- Azithromycin, a widely used antibiotic, has not been previously recognized for anti-angiogenic properties.
Purpose of the Study:
- To investigate azithromycin as a novel angiogenesis inhibitor for glioblastoma (GBM) treatment.
- To elucidate the mechanisms underlying azithromycin's anti-angiogenic effects.
- To evaluate the efficacy of azithromycin in preclinical GBM models.
Main Methods:
- In vitro assays using endothelial cells (ECs) to assess vessel structure formation, adhesion, growth, survival, and migration.
- In vivo studies using transgenic zebrafish (Tg (fli1a: EGFP)) to observe angiogenesis.
- In vivo efficacy studies in mouse models of GBM treated with azithromycin.
- Mechanistic studies involving mitochondrial respiration, ATP levels, and oxidative stress markers.
Main Results:
- Azithromycin inhibited vessel structure formation in GBM-derived and other ECs, particularly in early angiogenesis stages.
- Azithromycin reduced EC adhesion, growth, and survival, but not migration.
- In vivo, azithromycin significantly inhibited angiogenesis in zebrafish and reduced GBM tumor growth in mice at non-toxic doses, improving overall survival.
- Mechanistically, azithromycin suppressed mitochondrial respiration, reduced ATP, induced oxidative stress via thiol redox pathways, and damaged cells.
Conclusions:
- Azithromycin exhibits significant anti-angiogenic activity by inducing mitochondrial dysfunction and oxidative stress.
- Preclinical data support azithromycin's potential as a GBM therapeutic, warranting clinical trials.
- Azithromycin could be a valuable addition to standard-of-care treatments for glioblastoma patients.
More Related Videos
06:46Ortho- and Ectopic Zebrafish Xeno-Engraftment of Ocular Melanoma to Recapitulate Primary Tumor and Experimental Metastasis Development
Published on: September 4, 2021
09:23Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
