Kazımdirik, Ege Ünv. Hst. No:9, 35100 Bornova/Izmir, Turkey.
Kazımdirik, Ege Ünv. Hst. No:9, 35100 Bornova/Izmir, Turkey.
Gene. 2021 Apr 15;776:145445. doi: 10.1016/j.gene.2021.145445. Epub 2021 Jan 21.
Glioblastom Multiforme (GBM) is the most invasive and malignant member of the IV grade of the subclass Astrocytoma according to the last assessment of the 2016 WHO report. Due to the resistance to treatment and weak response, as well as the topographical structure of the blood brain barrier, the treatment is also difficult due to the severe clinical manifestation, and new treatment methods and new therapeutic agents are needed. Temozolomide (TMZ) is widely used in the treatment of glioblastoma and is considered as the primary treatment modality. TMZ, a member of the class of cognitive agents, is currently considered the most effective drug because it can easily pass through the blood brain barrier. Glucose metabolism is a complex energy producing machine that, a glucose molecule produces 38 molecules of ATP after full glycolytic catabolism. According to Otto Warburg's numerous studies cancer cells perform the first glycolytic step without entering the mitochondrial step. These cells produce lactic acid and make the micro-media more acidic even in aerobic conditions. This phenomenon is attributed to the Warburg hypothesis and either as aerobic glycolysis. Although glycolysis enzymes are the primary actors of this phenotypic expression, some genetic and epigenetic factors are no exception. We experimentally used KC7F2 active ingredient to target cancer metabolism. In our study, we evaluated cancer metabolism in combination with the effect of TMZ chemotherapeutic agent, examining the effect of two different agents separately and in combination to observe the effects of cancer cell proliferation, survival, apoptosis and expression of metabolism genes on expression. We observed that the combined effect of reduced the effective dose of the TMZ alkylating agent and that the effect was increased and the effect of the combined teraphy is assessed from a metabolic point of view and that it suppresses aerobic glycolysis.
多形性胶质母细胞瘤（GBM）是 2016 年世界卫生组织（WHO）报告中 IV 级星形细胞瘤子类中最具侵袭性和恶性的成员。由于治疗耐药性和反应较弱，以及血脑屏障的拓扑结构，由于临床表现严重，治疗也很困难，需要新的治疗方法和新的治疗药物。替莫唑胺（TMZ）广泛用于治疗胶质母细胞瘤，被认为是主要的治疗方式。TMZ 属于认知剂类，目前被认为是最有效的药物，因为它很容易穿过血脑屏障。葡萄糖代谢是一种复杂的能量产生机器，一个葡萄糖分子在完全糖酵解分解代谢后产生 38 个分子的 ATP。根据奥托·瓦尔堡（Otto Warburg）的大量研究，癌细胞在不进入线粒体步骤的情况下首先进行糖酵解步骤。这些细胞产生乳酸，使微环境在有氧条件下更加酸性。这种现象归因于沃伯格假说，也称为有氧糖酵解。尽管糖酵解酶是这种表型表达的主要因素，但一些遗传和表观遗传因素也不例外。我们实验性地使用 KC7F2 有效成分来靶向癌症代谢。在我们的研究中，我们结合 TMZ 化疗药物的作用评估了癌症代谢，分别评估了两种不同药物的单独和联合作用，观察它们对癌细胞增殖、存活、凋亡和代谢基因表达的影响。我们观察到联合作用降低了 TMZ 烷化剂的有效剂量，并且增加了效果，从代谢角度评估联合治疗的效果，并抑制有氧糖酵解。
