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Berberine radiosensitizes human nasopharyngeal carcinoma by suppressing hypoxia-inducible factor-1α expression
1Department of Radiotherapy, the First Affiliated Hospital of Nanjing Medical University , Nanjing, China.
Conclusion:
Berberine confers radiosensitivity on nasopharyngeal carcinoma (NPC) and this is associated with the down-regulation of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. Berberine could be a promising radiosensitizer for NPC radiotherapy.
Objectives:
NPC has a poor prognosis. Radiotherapy as first-line therapy significantly increases patient survival but radioresistance is a problem. This study aimed to investigate the radiosensitizing effects of berberine on NPC and explore the underlying mechanisms.
Methods:
CNE-1 and CNE-2 cells were exposed to hypoxia and treated with berberine at different concentrations. The MTT assay, clonogenic assay, and flow cytometry were performed to analyze cell proliferation, colony formation, and apoptosis. The expression of HIF-1α and VEGF was assessed by Western blot and immunofluorescence analysis. Male nude mice inoculated subcutaneously with CNE-2 cells were used to examine the sensitizing effects of berberine in vivo.
Results:
Berberine efficiently radiosensitized NPC cells and xenografts in mice, and inhibited hypoxia/radiation-induced up-regulation of HIF-1α and VEGF expression.
Insights
Berberine enhances radiotherapy effectiveness for nasopharyngeal carcinoma (NPC) by reducing hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). This natural compound shows promise as a radiosensitizer for NPC treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Nasopharyngeal carcinoma (NPC) presents a significant clinical challenge due to its poor prognosis.
- Radiotherapy is a primary treatment for NPC, but radioresistance limits its efficacy.
- Identifying agents to overcome radioresistance is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the radiosensitizing potential of berberine in NPC.
- To elucidate the molecular mechanisms underlying berberine's radiosensitizing effects.
- To evaluate berberine's efficacy both in vitro and in vivo.
Main Methods:
- NPC cell lines (CNE-1, CNE-2) were cultured under hypoxic conditions and treated with berberine.
- Cell proliferation, colony formation, and apoptosis were assessed using MTT, clonogenic, and flow cytometry assays.
- Hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression levels were analyzed via Western blot and immunofluorescence.
- In vivo studies utilized nude mouse xenograft models to evaluate berberine's radiosensitizing effects.
Main Results:
- Berberine demonstrated significant radiosensitization of NPC cells in vitro.
- Berberine treatment inhibited the hypoxia/radiation-induced upregulation of HIF-1α and VEGF.
- In vivo experiments confirmed that berberine enhances radiosensitivity in NPC xenografts.
- Berberine treatment reduced cell proliferation and induced apoptosis in NPC cells.
Conclusions:
- Berberine effectively confers radiosensitivity to nasopharyngeal carcinoma.
- The radiosensitizing effect is associated with the downregulation of HIF-1α and VEGF.
- Berberine represents a potential therapeutic agent as a radiosensitizer for NPC radiotherapy.
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