Alexanian Arshak, Stoellinger Heidi, De Araujo Farias Virginea, Quinones-Hinojosa Alfredo
Cell Reprogramming & Therapeutics LLC.
Mayo Clinic.
Res Sq. 2023 Mar 20:rs.3.rs-2698139. doi: 10.21203/rs.3.rs-2698139/v1.
Glioblastomas (GBM), also known as glioblastoma multiforme, are the most aggressive type of brain cancers. Currently, there is no real treatment for GBM and thus there is a compelling need for new therapeutic strategies for such type of cancers. Recently, we demonstrated that specific combinations of epigenetic modifiers significantly affect the metabolism and proliferation rate of two most aggressive GBM cell lines D54 and U-87. Importantly, these combinations exhibited minimal effect on normal stem cells growth. In this study we demonstrated that the combinations of modulators of histone and DNA covalent modifying enzymes that synergistically suppress D54 and U87 cell lines growth, also impair the viability of a patient freshly-derived GBM stem cell line. These data suggest that epigenetic modifiers alone or in specific combinations exhibit cytotoxic effect on established and low passage patient derived GB cell lines and thus could be a promising therapeutic approach for such type of brain cancers.
胶质母细胞瘤（GBM），也称为多形性胶质母细胞瘤，是最具侵袭性的脑癌类型。目前，对于GBM尚无有效的治疗方法，因此迫切需要针对此类癌症的新治疗策略。最近，我们证明表观遗传修饰剂的特定组合会显著影响两种最具侵袭性的GBM细胞系D54和U-87的代谢和增殖速率。重要的是，这些组合对正常干细胞生长的影响极小。在本研究中，我们证明了协同抑制D54和U87细胞系生长的组蛋白和DNA共价修饰酶调节剂组合，也会损害源自患者的新鲜GBM干细胞系的活力。这些数据表明，表观遗传修饰剂单独使用或特定组合对已建立的和低传代的源自患者的GB细胞系具有细胞毒性作用，因此可能是此类脑癌的一种有前景的治疗方法。
