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小檗碱通过抑制 TGF-β1/COL11A1 通路抑制神经胶质瘤细胞迁移和侵袭。

Berberine inhibits glioma cell migration and invasion by suppressing TGF-β1/COL11A1 pathway.

机构信息

Henan 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.

Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.

出版信息

Biochem Biophys Res Commun. 2022 Oct 15;625:38-45. doi: 10.1016/j.bbrc.2022.07.101. Epub 2022 Jul 31.

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.

摘要

脑胶质瘤是一种临床异质性疾病,预后不良。小檗碱(BBR)作为一种多靶点抗肿瘤生物碱,能够穿透血脑屏障,对脑胶质瘤细胞表现出细胞毒性。在之前的研究中,我们证明小檗碱通过抑制突变型 p53 蛋白和促进线粒体损伤来抑制脑胶质瘤细胞的增殖。此外,小檗碱已被证明可减少肺纤维化、糖尿病肾病和关节炎中的胶原积累。然而,它对癌症中胶原的影响需要进一步阐明。在这项研究中,我们证明了胶原 XI alpha 1 链(COL11A1)在脑胶质瘤细胞系中高度表达,并与脑胶质瘤细胞的迁移和侵袭有关。敲低 COL11A1 导致 MMPs 的表达减少。小檗碱通过抑制 TGF-β1/COL11A1 通路和改变肌动蛋白细胞骨架排列来抑制脑胶质瘤细胞的迁移和侵袭。裸鼠皮下异种移植模型也表明,小檗碱抑制了 COL11A1 在体内的表达。综上所述,以 COL11A1 为靶点抑制脑胶质瘤迁移和侵袭的小檗碱,可能成为未来开发抗脑胶质瘤药物的有前途的候选药物。

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