Dasatinib suppression of medulloblastoma survival and migration is markedly enhanced by combining treatment with the aurora kinase inhibitor AT9283.
Dasatinib suppression of medulloblastoma survival and migration is markedly enhanced by combining treatment with the aurora kinase inhibitor AT9283.
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DOI：
10.1016/j.canlet.2014.07.038
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发表时间：
2014-11-01
期刊：
影响因子：
9.7
通讯作者：
MacDonald, Tobey J.
中科院分区：
文献类型：
--
作者：
Petersen, William;Liu, Jingbo;Yuan, Liangping;Zhang, Hongying;Schneiderjan, Matthew;Cho, Yoon-Jae;MacDonald, Tobey J.
髓母细胞瘤（MB）表达Src激酶，而极光激酶A过表达与生存率低相关。因此，我们研究了新的组合治疗与达沙替尼和AT 9283，Src和极光激酶的抑制剂，分别对MB的生长在体外和体内。每种药物治疗均显著降低细胞活力，联合治疗显著增强了这种反应。AT 9283诱导p53表达、自噬和G2/M细胞周期阻滞，而联合给药诱导S期阻滞。达沙替尼治疗导致体内肿瘤消退。在分析的44% MB中检测到活化Src。我们的结论是，进一步评估这种联合治疗MB是非常必要的。
Medulloblastoma (MB) expresses Src kinase, while aurora kinase A overexpression correlates with poor survival. We thus investigated novel combination treatment with dasatinib and AT9283, inhibitors of Src and aurora kinase, respectively, on MB growth in vitro and in vivo. Treatment with each drug significantly reduced cell viability and combined treatment markedly potentiated this response. AT9283 induced p53 expression, autophagy, and G2/M cell-cycle arrest, while combined treatment induced S phase arrest. Dasatinib treatment caused tumor regression in vivo. Activated Src was detected in 44% MB analyzed. We conclude that further evaluation of this combination therapy for MB is highly warranted.
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影响因子：
3.9
作者：
Abouantoun, Thamara J.;Castellino, Robert C.;MacDonald, Tobey J.
通讯作者：
MacDonald, Tobey J.
影响因子：
50.5
作者：
Boss, D. S.;Witteveen, P. O.;Schellens, J. H.
通讯作者：
Schellens, J. H.
影响因子：
3.2
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Houghton, Peter J.
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46.9
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通讯作者：
Golub, Todd R.
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP