UNASSIGNED: The effect of AT9283 on the proliferation of BL cell lines was tested using the MTT assay. Apoptosis and cell cycle were measured by flow cytometry. The proteins associated with the cell cycle, apoptosis, and the Warburg effect were detected using Western blotting. Alterations in glycolytic metabolism in terms of glucose intake and lactate concentrations were determined by glucose and lactate assays.
UNASSIGNED: The current study utilized the GEPIA, the Human Protein Atlas (HAP) database and immunohistochemistry to conduct analyses, which revealed a high expression of Aurora kinases and Warburg effect-related proteins in malignant B-cell lymphoma tissues. AT9283 significantly inhibited the cell proliferation of BL cells and induced G2/M arrest. Additionally, AT9283 induced apoptosis in BL cells and reversed the Warburg effect by increasing glucose uptake and reducing lactate production. Moreover, the protein expression of hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A was significantly suppressed by AT9283, possibly through the inhibition of c-Myc and HIF-1α protein expression.
UNASSIGNED: The reversal of the Warburg effect in BL cells and the subsequent inhibition of cell proliferation and induction of apoptosis were observed by targeting Aurora A and Aurora B with AT9283. This finding may present new therapeutic options and targets for BL.
■使用MTT测定法测试了AT9283对BL细胞系增殖的影响。通过流式细胞术测量细胞凋亡和细胞周期。与细胞周期相关的蛋白质,凋亡,Warburg效应是用蛋白质印迹法检测的。通过葡萄糖和乳酸测定法确定糖酵解代谢在葡萄糖摄入量和乳酸浓度方面的变化。
■当前的研究利用了GEPIA,人类蛋白质图谱(HAP)数据库和免疫组织化学进行分析,揭示了Aurora激酶和Warburg效应相关蛋白在恶性B细胞淋巴瘤组织中的高表达。AT9283显著抑制BL细胞增殖并诱导G2/M期阻滞。此外,AT9283诱导BL细胞凋亡,并通过增加葡萄糖摄取和减少乳酸产生来逆转Warburg效应。此外,AT9283显著抑制己糖激酶2、丙酮酸激酶M2和乳酸脱氢酶A的蛋白表达,可能是通过抑制c-Myc和HIF-1α蛋白表达而实现的。
■通过用AT9283靶向AuroraA和AuroraB观察到BL细胞中Warburg效应的逆转以及随后对细胞增殖的抑制和凋亡的诱导。这一发现可能为BL提供新的治疗选择和靶标。