Exploring the role of Nrf2 signaling in glioblastoma multiforme.
Exploring the role of Nrf2 signaling in glioblastoma multiforme.
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DOI：
10.1007/s12672-022-00556-4
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发表时间：
2022-09-28
影响因子：
2.2
通讯作者：
Ashraf, Ghulam Md
中科院分区：
文献类型：
--
作者：
Awuah, Wireko Andrew;Toufik, Abdul-Rahman;Yarlagadda, Rohan;Mikhailova, Tatiana;Mehta, Aashna;Huang, Helen;Kundu, Mrinmoy;Lopes, Leilani;Benson, Sylvester;Mykola, Lyndin;Vladyslav, Sikora;Alexiou, Athanasios;Alghamdi, Badrah S.;Hashem, Anwar M.;Ashraf, Ghulam Md
多形性胶质母细胞瘤(GBM)是成人最具侵袭性的胶质细胞肿瘤之一。尽管目前对GBM的治疗方案提供了一些治疗益处，但中位存活率仍然很低，一般不会超过14个月。异柠檬酸脱氢酶(IDH)和O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)等基因与该病的发病机制有关，治疗通常根据IDH突变和MGMT启动子甲基化状态进行调整。最近的GBM细胞系研究表明，核因子红系相关因子2(Nrf2)的表达与高级别肿瘤有关。Nrf2的表达增加通常见于具有IDH-1突变的肿瘤。NRF2是一种重要的转录因子，具有抗凋亡、抗氧化、抗炎、增殖等多种功能，与多种调控途径相互作用复杂。此外，有证据表明，NRF2通过上调缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEC)，促进大鼠肾小球系膜细胞在低氧环境中的存活。下调Nrf2已被证明可以提高GBM对替莫唑胺等其他化疗药物的敏感性。因此，Nrf2可能是GBM途径的关键调节因子和潜在的治疗靶点。如果进一步研究Nrf2与主要分子信号转导机制之间的相互作用，可能会为新的GBM候选药物提供潜在的显著改善患者预后的机会。
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.
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