替莫唑胺治疗后真核起始因子表达减少——对神经胶质瘤治疗中的 eIF 具有潜在的新意义。
Decreased eukaryotic initiation factors expression upon temozolomide treatment-potential novel implications for eIFs in glioma therapy.
发表日期:2023 Oct 31
作者:
Stefanie Krassnig, Stefan L Leber, Andrea Orthmann, Nicole Golob-Schwarzl, Heinrich Johann Huber, Christina Wohlrab, Christina Skofler, Mirjam Pennauer, Andrea Raicht, Anna Maria Birkl-Toeglhofer, Michael Naumann, Kariem Mahdy-Ali, Gord von Campe, Marlene Leoni, Joshua Alcaniz, Jens Hoffmann, Thomas Wälchli, Serge Weis, Martin Benesch, Johannes Haybaeck
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
由于神经胶质瘤的治疗目前仍然有限,因此针对这一异质性肿瘤组的新治疗方案引起了人们的极大兴趣。真核起始因子(eIF)在包括神经胶质瘤在内的各种癌症实体中发生改变。我们研究的目的是评估 eIF 作为神经胶质瘤治疗新靶点的潜力。我们评估了 22 例胶质母细胞瘤患者来源的异种移植物 (GBM PDX) 在使用已确定的细胞抑制剂治疗后的 eIF 蛋白表达和调节,并进行了突变谱分析GBM PDX。我们观察到替莫唑胺 (TMZ) 治疗后几种 eIF 的表达降低,独立于磷脂酰肌醇 3-激酶 (PI3K)/AKT/雷帕霉素 (mTOR) 信号通路的哺乳动物靶标。 TMZ 治疗的这些作用在 TMZ 耐药的 PDX 中不存在。瑞戈非尼和 TMZ 的联合治疗重新建立了 eIF/AKT/mTOR 轴。我们的研究为胶质瘤 eIF 调节的化疗效果提供了新的见解,并表明 eIF 是未来改善胶质瘤治疗研究的有趣候选者。© 2023。作者(s)。
Since glioma therapy is currently still limited until today, new treatment options for this heterogeneous group of tumours are of great interest. Eukaryotic initiation factors (eIFs) are altered in various cancer entities, including gliomas. The purpose of our study was to evaluate the potential of eIFs as novel targets in glioma treatment.We evaluated eIF protein expression and regulation in 22 glioblastoma patient-derived xenografts (GBM PDX) after treatment with established cytostatics and with regards to mutation profile analyses of GBM PDX.We observed decreased expression of several eIFs upon temozolomide (TMZ) treatment independent from the phosphatidylinositol 3-kinase (PI3K)/ AKT/ mammalian target of the rapamycin (mTOR) signalling pathway. These effects of TMZ treatment were not present in TMZ-resistant PDX. Combination therapy of regorafenib and TMZ re- established the eIF/AKT/mTOR axis.Our study provides novel insights into chemotherapeutic effects on eIF regulation in gliomas and suggests that eIFs are interesting candidates for future research to improve glioma therapy.© 2023. The Author(s).