Mechanism of Baclofen Inhibiting the Proliferation and Metastasis of GBM by Regulating YAP

Lin Zhu,Zhijun Bao,Shiwen Guo,Juan Lu,Weiguo Li

doi:10.1155/2021/2753571

Abstract

This study explores the effect of baclofen on the malignant phenotype of glioblastoma (GBM) and the growth of xenograft tumors and investigates the related mechanisms, aiming to reveal the effect of baclofen on the occurrence and development of GBM. The development of new therapeutic drugs for GBM lays a theoretical and experimental foundation. Research results show that baclofen could inhibit GBM cell proliferation and migration and promote GBM cell apoptosis; baclofen dose- and time-dependently could induce GBM cell YAP phosphorylation. YAP participated in the effect of baclofen on GBM cell proliferation and migration inhibition. Baclofen induced YAP phosphorylation in GBM cells through the GABABR2-Gs-Lats1/2 signaling pathway. Baclofen could inhibit the expression of survivin and Bcl2. Baclofen inhibits subcutaneous tumors by inducing YAP phosphorylation in vivo.

Highlights

Glioma is the most important and common central nervous system tumor and fatal primary brain tumor [1]
In order to investigate the function of baclofen, we treated GBM cells (U251) with 10, 50, 100, and 120 μM baclofen for 18 hours
We treated U251 cell line with 10, 50, 100, and 120 μM baclofen, respectively. e results turned out that YAP phosphorylation was induced when treated with 50 μM baclofen; besides, 100 μM baclofen was the optimal concentration in inducing the phosphorylation of YAP (Figure 3(a))

Summary

Introduction

Glioma is the most important and common central nervous system tumor and fatal primary brain tumor [1]. Chemotherapy, and surgery have made great progress in the treatment of tumors, the prognosis of malignant GBM is still very poor, and the average survival time of patients is less than 1.5 years [3]. E molecular mechanism of GBM is a multistep development process of multigene changes [4]. With the further understanding of the molecular pathways driving malignant tumors in malignant GBM, various biomarkers and several drugs targeting specific molecular pathways in malignant cells have been developed. Despite the progress of current treatment, the prognosis of GBM is still poor, and the median survival time is only 12–15 months [7, 8]. In GBM, rapid tumor development and resistance to chemotherapy and radiotherapy are common, resulting in low 1-year survival. In GBM, rapid tumor development and resistance to chemotherapy and radiotherapy are common, resulting in low 1-year survival. erefore, further research is needed to explore the molecular mechanism of glioma progression and find new and effective glioma treatment strategies

Methods

Results

Conclusion