de Faria Fernanda Costas C, Leal Maria Eduarda Bento, Bernardo Paula Sabbo, Costa Paulo R R, Maia Raquel C
Anticancer Agents Med Chem. 2015;15(3):345-52. doi: 10.2174/18715206113139990108.
Chronic myeloid leukemia (CML), a myeloproliferative disorder characterized by the BCR-ABL oncoprotein, presents its treatment based on tyrosine kinase inhibitors (TKIs), mainly imatinib. However, despite its clinical success, almost 30% of all CML patients demand alternative therapy. In this context, the development of drugs capable of overcoming TKIs resistance is imperative. The pterocarpanquinone-LQB-118 is a novel compound with anti-tumor effect in CML cells whose mechanism of action is being elucidated. Here, we demonstrate that in two CML cell lines exhibiting different biological characteristics, LQB-118 modulates NFκB subcellular localization, apparently independently of the AKT and MAPK pathways, partially inhibits proteasome activity, and alters the expression of microRNAs -9 and -21.
慢性粒细胞白血病（CML）是一种以BCR-ABL癌蛋白为特征的骨髓增殖性疾病，其治疗主要基于酪氨酸激酶抑制剂（TKIs），主要是伊马替尼。然而，尽管在临床上取得了成功，但几乎30%的CML患者需要替代疗法。在这种情况下，开发能够克服TKIs耐药性的药物势在必行。紫檀醌-LQB-118是一种在CML细胞中具有抗肿瘤作用的新型化合物，其作用机制正在阐明。在这里，我们证明，在两种表现出不同生物学特性的CML细胞系中，LQB-118调节NFκB亚细胞定位，显然独立于AKT和MAPK途径，部分抑制蛋白酶体活性，并改变microRNAs -9和-21的表达。
