PDF(Pubmed)
Abstract：
Glioblastoma multiforme (GBM) is one of the most aggressive glial cell tumors in adults. Although current treatment options for GBM offer some therapeutic benefit, median survival remains poor and does not generally exceed 14 months. Several genes, such as isocitrate dehydrogenase (IDH) enzyme and O6-methylguanine-DNA methyltransferase (MGMT), have been implicated in pathogenesis of the disease. Treatment is often adapted based on the presence of IDH mutations and MGMT promoter methylation status. Recent GBM cell line studies have associated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) expression with high-grade tumors. Increased Nrf2 expression is often found in tumors with IDH-1 mutations. Nrf2 is an important transcription factor with anti-apoptotic, antioxidative, anti-inflammatory, and proliferative properties due to its complex interactions with multiple regulatory pathways. In addition, evidence suggests that Nrf2 promotes GBM cell survival in hypoxic environment,by up-regulating hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Downregulation of Nrf2 has been shown to improve GBM sensitivity to chemotherapy drugs such as Temozolomide. Thus, Nrf2 could be a key regulator of GBM pathways and potential therapeutic target. Further research efforts exploring an interplay between Nrf2 and major molecular signaling mechanisms could offer novel GBM drug candidates with a potential to significantly improve patients prognosis.
摘要：
多形性胶质母细胞瘤(GBM)是成人中最具侵袭性的胶质细胞肿瘤之一。虽然目前GBM的治疗方案提供了一些治疗益处，中位生存期仍然较差,一般不超过14个月.几个基因，如异柠檬酸脱氢酶（IDH）酶和O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT），与该疾病的发病机理有关。通常基于IDH突变的存在和MGMT启动子甲基化状态来调整治疗。最近的GBM细胞系研究已经将核因子红系2相关因子2(Nrf2)表达与高级别肿瘤相关联。通常在具有IDH-1突变的肿瘤中发现Nrf2表达增加。Nrf2是一种重要的抗凋亡转录因子,抗氧化，抗炎,和增殖特性，由于其与多种调节途径的复杂相互作用。此外,证据表明，Nrf2促进GBM细胞在低氧环境中的存活，通过上调缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)。Nrf2的下调已显示可改善GBM对化疗药物如替莫唑胺的敏感性。因此，Nrf2可能是GBM途径的关键调节因子和潜在的治疗靶点。进一步的研究努力探索Nrf2和主要分子信号传导机制之间的相互作用可以提供新型GBM候选药物，具有显着改善患者预后的潜力。
