Src family kinase inhibitor bosutinib enhances retinoic acid-induced differentiation of HL-60 leukemia cells.
Src family kinase inhibitor bosutinib enhances retinoic acid-induced differentiation of HL-60 leukemia cells.
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DOI：
10.1080/10428194.2018.1452213
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发表时间：
2018-12
影响因子：
2.6
通讯作者：
Yen A
中科院分区：
文献类型：
--
作者：
MacDonald RJ;Bunaciu RP;Ip V;Dai D;Tran D;Varner JD;Yen A
急性早幼粒细胞白血病（APL）已经用全反式维甲酸（RA）治疗了几十年。虽然RA在非apl AML亚型中基本上无效，但RA和其他药物的联合治疗目前正在临床试验中。利用ra反应性非apl AML细胞系HL-60，我们测试了Src家族激酶（SFK）抑制剂博舒替尼对ra诱导的分化的疗效。HL-60最近被证明对一种对RA有反应的AML亚型具有保真性。我们发现RA和博舒替尼联合治疗增强了分化，CD11b表达增加，G1/G0细胞周期阻滞和呼吸爆发。SFK成员Fgr和Lyn的表达增强，而SFK的激活被抑制。c-Raf几个位点的磷酸化增加，AhR和p85 PI3K的表达增强。c-Cbl和mTOR表达降低。我们的研究表明SFK抑制增强了ra诱导的分化，可能对非apl AML具有治疗价值。
The acute promyelocytic leukemia (APL) has been treated with all-trans retinoic acid (RA) for decades. While RA has largely been ineffective in non-APL AML subtypes, co-treatments combining RA and other agents are currently in clinical trials. Using the RA-responsive non-APL AML cell line HL-60, we tested the efficacy of the Src family kinase (SFK) inhibitor bosutinib on RA-induced differentiation. HL-60 has been recently shown to bear fidelity to a subtype of AML that respond to RA. We found that co-treatment with RA and bosutinib enhanced differentiation evidenced by increased CD11b expression, G1/G0 cell cycle arrest, and respiratory burst. Expression of the SFK members Fgr and Lyn was enhanced, while SFK activation was inhibited. Phosphorylation of several sites of c-Raf was increased and expression of AhR and p85 PI3K was enhanced. Expression of c-Cbl and mTOR was decreased. Our study suggests that SFK inhibition enhances RA-induced differentiation and may have therapeutic value in non-APL AML.
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影响因子：
11.2
作者：
Bunaciu RP;Yen A
通讯作者：
Yen A
影响因子：
2.6
作者：
Ibabao, Christopher N.;Bunaciu, Rodica P.;Schaefer, Deanna M. W.;Yen, Andrew
通讯作者：
Yen, Andrew
影响因子：
--
作者：
Bunaciu RP;MacDonald RJ;Gao F;Johnson LM;Varner JD;Wang X;Nataraj S;Guzman ML;Yen A
通讯作者：
Yen A
影响因子：
5.7
作者：
Vultur, Adina;Buettner, Ralf;Jove, Richard
通讯作者：
Jove, Richard
影响因子：
11.4
作者：
通讯作者：
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