He Xiu-Ying, Yang Yui-Si, Zheng Yue-Xiang, Xia Qing-Jie, Yu Hong-Zhou, Zhao Xiao-Ming, Wang Ting-Hua
Department of Anesthesiology, Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu, China.
School of Integrated Traditional Chinese and Western medicine, Southwest Medical University, Luzhou, China.
PLoS One. 2025 Jan 31;20(1):e0318031. doi: 10.1371/journal.pone.0318031. eCollection 2025.
Glioma is the most common primary intracranial tumors. Although great achievements have been made in the treatment, the efficacy is still unsatisfactory, which imposes a hefty burden on patients and society. Therefore, the exploration of new and effective anti-glioma drugs is urgent.
Human glioma cell lines U251 and LN229 were included in the study. Cell proliferation was detected by cell counting kit-8 (CCK8), plate clone formation assay, EdU incorporation assay and xCELLigence real-time cell analyzer. Cell apoptosis was evaluated by TUNEL assay and flow cytometry. Then, transwell assay was used for assessing the migration. Moreover, tumor xenograft model was established to examine the effect of scutellarin (SCU) and lidocaine on the growth of glioma in vivo. Lastly, western blot was performed to detect the protein level of epidermal growth factor receptor (EGFR).
In present study, we found that SCU and lidocaine suppressed the proliferation and migration, and induced the apoptosis of human glioma cell lines, including U251 and LN229 cells, in a dose-dependent manner in vitro. Moreover, the combination of SCU and lidocaine further restrained the proliferation and migration ability of U251 and LN229 cells, while induced their apoptosis in vitro. Additionally, SCU and lidocaine also inhibited the growth of glioma in vivo, and the effect of the combination was better. Above all, the toxicity of SCU and its combination with lidocaine was low to normal astrocytes and neurons. Mechanistically, the effect of SCU and its combination with lidocaine on glioma cells was partially associated with the repression of EGFR signaling.
Scutellarin and lidocaine exerted a synergistic effect on suppressing the proliferation and migration and inducing the apoptosis of glioma cells, which was partly associated with the repression of EGFR signaling.
胶质瘤是最常见的原发性颅内肿瘤。尽管在治疗方面已取得巨大成就，但疗效仍不尽人意，给患者和社会带来沉重负担。因此，探索新的有效抗胶质瘤药物迫在眉睫。
本研究纳入人胶质瘤细胞系U251和LN229。通过细胞计数试剂盒-8（CCK8）、平板克隆形成试验、EdU掺入试验和xCELLigence实时细胞分析仪检测细胞增殖。通过TUNEL试验和流式细胞术评估细胞凋亡。然后，采用Transwell试验评估迁移能力。此外，建立肿瘤异种移植模型以检测灯盏花素（SCU）和利多卡因对体内胶质瘤生长的影响。最后，进行蛋白质印迹法检测表皮生长因子受体（EGFR）的蛋白水平。
在本研究中，我们发现SCU和利多卡因在体外以剂量依赖性方式抑制人胶质瘤细胞系（包括U251和LN229细胞）的增殖和迁移，并诱导其凋亡。此外，SCU和利多卡因联合使用进一步抑制U251和LN229细胞的增殖和迁移能力，同时在体外诱导其凋亡。另外，SCU和利多卡因在体内也抑制胶质瘤的生长，联合使用效果更佳。最重要的是，SCU及其与利多卡因联合使用对正常星形胶质细胞和神经元的毒性较低。机制上，SCU及其与利多卡因联合使用对胶质瘤细胞的作用部分与EGFR信号通路的抑制有关。
灯盏花素和利多卡因在抑制胶质瘤细胞增殖和迁移以及诱导其凋亡方面发挥协同作用，这部分与EGFR信号通路的抑制有关。
