Berberine Inhibits Glioma Cell Migration and Invasion by Suppressing TGF-β1/COL11A1 Pathway and Enhances Chemosensitivity

Abstract Background: The expression of collagen type XI alpha 1 chain (COL11A1) is up-regulated in many cancers, affecting the risk of metastasis, drug resistance, and poor prognosis. Berberine is an isoquinoline alkaloid present in many traditional Chinese medicines and it has been shown to reduce collagen accumulation in pulmonary fibrosis, diabetic nephropathy and arthritis. However, its effect on COL11A1 in glioma needs to be further elucidated.Methods: Western blot was performed to detect the expression level of COL11A1 in several glioma cells, and siCOL11A1 was performed to investigate the effect of COL11A1 on the migration and invasion ability of glioma cells. CCK-8, wound healing experiment and transwell experiment were performed to detect the effect of berberine on the proliferation, migration and invasion of glioma cells. The xenografts experiment in nude mice was performed to test the effect of berberine on inhibiting glioma in vivo.Results: Our results showed that COL11A1 is highly expressed in glioma cell lines and associated with migration, invasion, and chemoresistance of glioma cells. Knocking down COL11A1 caused decreased expression of MMPs, Snail, and MGMT. Berberine could inhibit the migration and invasion of glioma cells by suppressing the TGF-β1/COL11A1 pathway and changes actin cytoskeleton arrangement. In addition, berberine increased the chemosensitivity of glioma cells to temozolomide, which may be related to the down-regulation of Snail and MGMT proteins caused by berberine. High-throughput sequencing of xenografts in nude mice also showed that berberine inhibited the expression of COL11A1 in vivo.Conclusions: Our results suggest that berberine that targets COL11A1 to inhibit glioma migration, invasion and chemoresistance, may serve as a promising candidate for the development of anti-glioma drugs in the future.