In Vitro Experiment Present ROCK2 Inhibition Promotes the Therapeutic Effect of Bevacizumab in the Treatment of Glioblastoma Multiforme.

IF 0.8 4区医学 Q4 CLINICAL NEUROLOGY

Clinical Neuropharmacology Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI:10.1097/WNF.0000000000000613

Jun Lai, Xiaojing Zhang, Kaixin Liang

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引用次数: 0

Abstract

Objective: Gliomas are a general designation for neuroepithelial tumors derived from the glial cells of the central nervous system. According to the histopathological and immunohistochemical features, the World Health Organization classifies gliomas into four grades. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor that has been approved for the treatment of glioblastoma multiforme (GBM) as a second-line therapy. However, its efficacy remains limited. Rho/Rho-associated kinase (ROCK) is a downstream molecule of small guanosine triphosphatases (GTPases) that regulates multiple cellular processes, including motility, migration, and proliferation. Thus, ROCK has been regarded as a therapeutic target for cardiovascular diseases, neurological diseases, immune diseases, and cancer, and ROCK inhibitors have high potential clinical value.

Methods: Viability rate of cells was detected using MTT assay, and apoptosis of cells was detected using FACS. Expression of target genes and proteins was detected using qPCR and western blotting analysis. Concentration of cytokines was detected using ELISA methods.

Results: Viability and migration of GBM cells were reduced after bevacizumab treatment and that these effects were enhanced by ROCK2 inhibition. We further found that ROCK2 inhibition promoting the effect of bevacizumab was mainly mediated by the RhoA/ROCK2 pathway, further inducing apoptosis in GBM cells. In addition, we found that angiogenesis and degradation of cellular matrix-related cytokines were reduced by ROCK2 inhibition.

Conclusions: ROCK2 inhibition contributes to the therapeutic effects of bevacizumab.

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体外实验表明，抑制ROCK2可促进贝伐单抗治疗多形性胶质母细胞瘤的疗效。

目的：神经胶质瘤是来源于中枢神经系统胶质细胞的神经上皮肿瘤的总称。根据组织病理学和免疫组织化学特征，世界卫生组织将胶质瘤分为四个等级。贝伐单抗是一种靶向血管内皮生长因子的单克隆抗体，已被批准用于多形性胶质母细胞瘤（GBM）的二线治疗。然而，它的功效仍然有限。Rho/Rho相关激酶（ROCK）是小鸟苷三磷酸酶（GTPases）的下游分子，调节多种细胞过程，包括运动、迁移和增殖。因此，ROCK已被视为心血管疾病、神经系统疾病、免疫疾病和癌症的治疗靶点，ROCK抑制剂具有很高的潜在临床价值。方法：采用MTT法检测细胞存活率，流式细胞仪检测细胞凋亡。采用qPCR和western blotting检测靶基因和蛋白的表达。ELISA法检测细胞因子浓度。结果：贝伐单抗治疗后GBM细胞的活力和迁移能力降低，抑制ROCK2可增强这些作用。我们进一步发现，促进贝伐单抗作用的ROCK2抑制主要通过RhoA/ROCK2通路介导，进一步诱导GBM细胞凋亡。此外，我们发现ROCK2抑制可降低血管生成和细胞基质相关细胞因子的降解。结论：抑制ROCK2有助于贝伐单抗的治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Neuropharmacology 医学-临床神经学

CiteScore

1.20

自引率

10.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical Neuropharmacology is a peer-reviewed journal devoted to the pharmacology of the nervous system in its broadest sense. Coverage ranges from such basic aspects as mechanisms of action, structure-activity relationships, and drug metabolism and pharmacokinetics, to practical clinical problems such as drug interactions, drug toxicity, and therapy for specific syndromes and symptoms. The journal publishes original articles and brief reports, invited and submitted reviews, and letters to the editor. A regular feature is the Patient Management Series: in-depth case presentations with clinical questions and answers.