Zhao Linyao, Wang Yixuan, Xu Yang, Sun Qian, Liu Hao, Chen Qianxue, Liu Baohui
Department of Neurosurgery, Renmin Hospital of Wuhan University, Hubei 430060, China.
Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, PR China.
ACS Omega. 2021 Apr 22;6(17):11466-11473. doi: 10.1021/acsomega.1c00521. eCollection 2021 May 4.
Glioblastoma (GBM) is the most common malignant tumor, and it is characterized by high cellular proliferation and invasion in the central nervous system of adults. Due to its high degree of heterogeneity and mortality, there is no effective therapy for GBM. In our study, we investigated the effect of the p38-MAPK signaling pathway inhibitor BIRB796 on GBM cells. Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EDU) staining, and cell cycle distribution analysis were performed, and the results showed that BIRB796 decreased proliferation in U87 and U251 cells. Moreover, wound healing and invasion assays were performed, which showed that BIRB796 inhibited the migration and invasion of human GBM cells. We found that BIRB796 treatment significantly decreased the formation of the cytoskeleton and thus downregulated the movement ability of the cells, as shown by phalloidin staining and vimentin immunofluorescence staining. Real-time polymerase chain reaction showed that the mRNA levels of MMP-2, Vimentin, CyclinD1, and Snail-1 were downregulated. Consistently, the expressions of MMP-2, Vimentin, CyclinD1, and p-p38 were also decreased after BIRB796 treatment. Taken together, all our results demonstrated that BIRB796 could play an antitumor role by inhibiting the proliferation and invasion in GBM cells. Thus, BIRB796 may be used as an adjuvant therapy to improve the therapeutic efficacy of GBM treatment.
胶质母细胞瘤（GBM）是最常见的恶性肿瘤，其特征是在成人大脑中具有高细胞增殖和侵袭能力。由于其高度的异质性和死亡率，目前尚无针对GBM的有效治疗方法。在我们的研究中，我们研究了p38丝裂原活化蛋白激酶（MAPK）信号通路抑制剂BIRB796对GBM细胞的影响。进行了细胞计数试剂盒-8（CCK-8）检测、5-乙炔基-2'-脱氧尿苷（EDU）染色和细胞周期分布分析，结果表明BIRB796降低了U87和U251细胞的增殖。此外，进行了伤口愈合和侵袭试验，结果表明BIRB796抑制了人GBM细胞的迁移和侵袭。我们发现，鬼笔环肽染色和波形蛋白免疫荧光染色显示，BIRB796处理显著减少了细胞骨架的形成，从而下调了细胞的运动能力。实时聚合酶链反应显示，基质金属蛋白酶-2（MMP-2）、波形蛋白、细胞周期蛋白D1（CyclinD1）和Snail-1的mRNA水平下调。一致地，BIRB796处理后，MMP-2、波形蛋白、CyclinD1和磷酸化p38的表达也降低。综上所述，我们所有的结果表明，BIRB796可以通过抑制GBM细胞的增殖和侵袭发挥抗肿瘤作用。因此，BIRB796可作为辅助治疗药物，提高GBM治疗的疗效。
