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Published on: February 24, 2021
Berberine inhibits glioma cell migration and invasion by suppressing TGF-β1/COL11A1 pathway
Yuxue Sun1, Haiyan Huang2, Zhixin Zhan2
1Henan Provincial People's Hospital, Cerebrovascular Disease Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China; Henan Provincial People's Hospital, Cerebrovascular disease hospital, People's Hospital of Henan University, Zhengzhou, Henan, 450003, China; Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Abstract:
Glioma is a clinically heterogeneous disease with a poor prognosis. Berberine (BBR), as a multi-target anti-tumor alkaloid, has the ability to penetrate the blood-brain barrier and shows cytotoxicity to glioma cells. In previous studies, we demonstrated that berberine inhibits glioma cell proliferation by inhibiting mutant p53 protein and promoting mitochondrial damage. In addition, berberine has been shown to reduce collagen accumulation in pulmonary fibrosis, diabetic nephropathy and arthritis. However, its effect on collagen in cancer needs to be further elucidated. In this study, we proved that the collagen XI alpha 1 chain (COL11A1) is highly expressed in glioma cell lines and associated with migration and invasion of glioma cells. Knocking down COL11A1 caused decreased expression of MMPs. Berberine could inhibit the migration and invasion of glioma cells by suppressing the TGF-β1/COL11A1 pathway and changes actin cytoskeleton arrangement. Nude mouse subcutaneous xenografts model also showed that berberine inhibited the expression of COL11A1 in vivo. Collectively, berberine that targets COL11A1 to inhibit glioma migration and invasion, may serve as a promising candidate for the development of anti-glioma drugs in the future.
Insights
Berberine inhibits glioma cell migration and invasion by targeting collagen XI alpha 1 chain (COL11A1). This natural compound shows promise as a future anti-glioma drug by impacting the TGF-β1/COL11A1 pathway.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Glioma is a heterogeneous cancer with poor prognosis.
- Berberine (BBR) exhibits anti-tumor properties and penetrates the blood-brain barrier.
- Previous research shows BBR inhibits glioma proliferation and affects collagen in other diseases.
Purpose of the Study:
- To investigate the role of collagen XI alpha 1 chain (COL11A1) in glioma.
- To elucidate the mechanism by which berberine affects glioma cell migration and invasion.
- To evaluate berberine as a potential therapeutic agent for glioma.
Main Methods:
- Assessed COL11A1 expression in glioma cell lines.
- Investigated the effect of COL11A1 knockdown on matrix metalloproteinases (MMPs).
- Examined berberine's impact on glioma cell migration, invasion, TGF-β1/COL11A1 pathway, and actin cytoskeleton.
- Validated findings in a nude mouse subcutaneous xenograft model.
Main Results:
- COL11A1 was highly expressed in glioma cells and linked to increased migration and invasion.
- COL11A1 knockdown reduced MMP expression.
- Berberine suppressed glioma cell migration and invasion by inhibiting the TGF-β1/COL11A1 pathway and altering actin cytoskeleton.
- Berberine reduced COL11A1 expression in vivo.
Conclusions:
- COL11A1 is a key driver of glioma cell migration and invasion.
- Berberine effectively inhibits glioma progression by targeting the TGF-β1/COL11A1 pathway.
- Berberine is a promising candidate for developing novel anti-glioma therapies.
