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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

针对人髓母细胞瘤细胞中STAT3的上游激酶

卷 19, 期 7, 2019

页: [571 - 582] 页: 12

弟呕挨: 10.2174/1568009618666181016165604

价格: $65

摘要

背景：髓母细胞瘤是儿童中最常见的恶性脑肿瘤。 尽管总体存活率有所提高，但仍缺乏有效的靶向治疗策略。 Janus家族的细胞质酪氨酸激酶（JAKs）和Src激酶，信号转导和转录激活因子3（STAT3）的上游蛋白激酶，在髓母细胞瘤发病机制中起重要作用，因此代表潜在的治疗靶点。 方法：在本报告中，我们检测了JAK1 / 2抑制剂，ruxolitinib，JAK3抑制剂，tofacitinib和两种Src抑制剂KX2-391和达沙替尼的抑制效果。 结果：这些小分子药物在体外显着降低细胞活力，抑制人髓母细胞瘤细胞的细胞迁移和集落形成。 Src抑制剂在抑制髓母细胞瘤细胞迁移能力方面比JAK抑制剂具有更强的功效。 Src抑制剂可以抑制STAT3和Src的磷酸化，而JAK抑制剂可以抑制JAK / STAT3的磷酸化。 我们还研究了Src抑制剂达沙替尼与顺铂的联合作用。 结果表明，达沙替尼通过抑制STAT3和Src，在人髓母细胞瘤细胞中与顺铂发挥协同作用。 结论：我们的研究结果表明，STAT3上游激酶，ruxolitinib，tofacitinib，KX2-391和达沙替尼的小分子抑制剂可能是治疗人髓母细胞瘤的新型和有吸引力的候选药物。

关键词: 髓母细胞瘤，Src抑制剂，JAK抑制剂，STAT3，达沙替尼，顺铂。

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