Stewart Helen J S, Chaudry Sabah, Crichlow Asante, Luiling Feilding Freya, Chevassut Timothy J T
Research Building, Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9PS, UK.
Bone Marrow Res. 2018 May 31;2018:5742954. doi: 10.1155/2018/5742954. eCollection 2018.
S100A8 and S100A9 are both members of the S100 family and have been shown to play roles in myeloid differentiation, autophagy, apoptosis, and chemotherapy resistance. In this study we demonstrate that the BET-bromodomain inhibitor JQ1 causes rapid suppression of and mRNA and protein in a reversible manner. In addition, we show that JQ1 synergises with daunorubicin in causing AML cell death. Daunorubicin alone causes a dose- and time-dependent increase in S100A8 and S100A9 protein levels in AML cell lines which is overcome by cotreatment with JQ1. This suggests that JQ1 synergises with daunorubicin in causing apoptosis via suppression of S100A8 and S100A9 levels.
S100A8和S100A9都是S100家族的成员，已被证明在髓系分化、自噬、凋亡和化疗耐药中发挥作用。在本研究中，我们证明BET-溴结构域抑制剂JQ1以可逆方式导致S100A8和S100A9 mRNA及蛋白的快速抑制。此外，我们表明JQ1与柔红霉素协同作用导致AML细胞死亡。单独使用柔红霉素会导致AML细胞系中S100A8和S100A9蛋白水平呈剂量和时间依赖性增加，而与JQ1联合处理可克服这一现象。这表明JQ1与柔红霉素协同作用，通过抑制S100A8和S100A9水平导致细胞凋亡。
