Department of Pediatric Laboratory, The Affiliated Wuxi Children's Hospital of Nanjing Medical University, Wuxi, 214000, Jiangsu, China.
Department of Hematology & Oncology, The Affiliated Wuxi Children's Hospital of Nanjing Medical University, Wuxi, 214000, Jiangsu, China.
Med Oncol. 2022 Dec 8;40(1):44. doi: 10.1007/s12032-022-01899-2.
Glycogen Synthase Kinase-3 (GSK-3) was recently implicated in the dysregulated biology of acute myeloid leukemia (AML). Low concentrations of GSK-3 inhibitors, SB216763 and BIO, suppressed the proliferation of AML cells with FLT3-ITD as early as 24 h after treatment. BIO was used in subsequent assays since it exhibited higher inhibitory effects than SB216763. BIO-induced G1 cell cycle arrest by regulating the expression of cyclin D2 and p21 in MV4-11 cells, and promoted apoptosis by regulating the cleaved-caspase3 signaling pathways. In vivo assays demonstrated that BIO suppressed tumor growth, while metabolomics assay showed that BIO reduced the levels of ATP and pyruvate in MV4-11 cells suggesting that it inhibited glycolysis. BIO markedly suppressed cell growth and induced apoptosis of AML cells with FLT3-ITD by partially inhibiting glycolysis, suggesting that BIO may be a promising therapeutic candidate for AML.
糖原合酶激酶-3（GSK-3）最近被牵连到急性髓系白血病（AML）失调的生物学中。低浓度的 GSK-3 抑制剂 SB216763 和 BIO，在治疗后 24 小时内就可抑制具有 FLT3-ITD 的 AML 细胞的增殖。由于 BIO 比 SB216763 具有更高的抑制作用，因此在后续的实验中使用 BIO。BIO 通过调节 MV4-11 细胞中环蛋白 D2 和 p21 的表达诱导 G1 细胞周期停滞，并通过调节裂解型 caspase3 信号通路促进细胞凋亡。体内实验表明 BIO 抑制肿瘤生长，而代谢组学实验表明 BIO 降低 MV4-11 细胞中 ATP 和丙酮酸的水平，提示其抑制糖酵解。BIO 通过部分抑制糖酵解显著抑制具有 FLT3-ITD 的 AML 细胞的生长并诱导其凋亡，表明 BIO 可能是 AML 的一种有前途的治疗候选药物。
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