Zhou Lu, Liang Hongsheng, Nie Chenyi, Zhou Jiaxin, Li Kuo, Zhang Xi, Xu Jiahang, Hu Renjie, Gao Aili
Northeast Agricultural University, Harbin, 150000, China.
Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Appl Biochem Biotechnol. 2025 Aug 20. doi: 10.1007/s12010-025-05341-x.
Glioma is the most common and aggressive primary adult brain tumor. Furthermore, the prognosis for glioma patients following chemoradiotherapy is unfavourable due to the inherent anti-apoptotic characteristics of glioma cells. Thus, the treatment of gliomas remains a challenge. Our aim was to define the molecular mechanisms underlying the effects of TXN1 on the anti-apoptotic ability and proliferation of glioma cells. The relationship between TXN1 expression and glioma patients was initially predicted using bioinformatics methods and then verified through clinical glioma tissue Results showed that the expression of TXN1 increases with the malignant degree of glioma, leading to a worse prognosis for patients.Then glioma cells were treated with lentivirus to be stable cell lines with suppressed TXN1 expression. MTT, flow cytometry, immunofluorescence, western blot and qRT-PCR were used to analyse changes in glioma proliferation, cell cycle, apoptosis and the expressioin of the P38 MAPK signaling pathway. Moreover,the expression levels of related proteins in the transplanted tumor tissues of nude mice were investigated by immunohistochemistry. Reducing TXN1 expression caused glioma cell cycle in G2/M phase, increased cell apoptosis rate and mitochondrial membrane damage. Furthermore, this was correlated with activity of the P38 MAPK pathway. Reduction of TXN1 expression can activate the P38 MAPK pathway to cause glioma cell cycle arrest and induce mitochondrial apoptosis. This study revealed for the first time that inhibition of TXN1 can destroy the apoptotic resistance mechanism of glioma by activating ASK1/P38 MAPK axis, resulting in G2/M phase arrest of glioma cells, inhibiting the proliferation of glioma cells, and promoting apoptosis of glioma cells in malignant gliomas. Combining TXN1 inhibitors with radiotherapy and chemotherapy is expected to significantly improve the clinical prognosis of glioma patients.
胶质瘤是最常见且侵袭性最强的原发性成人脑肿瘤。此外，由于胶质瘤细胞固有的抗凋亡特性，胶质瘤患者放化疗后的预后不佳。因此，胶质瘤的治疗仍然是一项挑战。我们的目的是确定TXN1对胶质瘤细胞抗凋亡能力和增殖影响的分子机制。首先使用生物信息学方法预测TXN1表达与胶质瘤患者之间的关系，然后通过临床胶质瘤组织进行验证。结果显示，TXN1的表达随胶质瘤恶性程度增加而升高，导致患者预后更差。然后用慢病毒处理胶质瘤细胞，使其成为TXN1表达受抑制的稳定细胞系。采用MTT法、流式细胞术、免疫荧光法、蛋白质免疫印迹法和qRT-PCR法分析胶质瘤增殖、细胞周期、凋亡及P38 MAPK信号通路表达的变化。此外，通过免疫组织化学研究裸鼠移植瘤组织中相关蛋白的表达水平。降低TXN1表达导致胶质瘤细胞周期停滞于G2/M期，增加细胞凋亡率并损伤线粒体膜。此外，这与P38 MAPK通路的活性相关。降低TXN1表达可激活P38 MAPK通路，导致胶质瘤细胞周期停滞并诱导线粒体凋亡。本研究首次揭示，抑制TXN1可通过激活ASK1/P38 MAPK轴破坏胶质瘤的凋亡抵抗机制，导致胶质瘤细胞G2/M期停滞，抑制胶质瘤细胞增殖，并促进恶性胶质瘤中胶质瘤细胞的凋亡。将TXN1抑制剂与放疗和化疗联合使用有望显著改善胶质瘤患者的临床预后。
