抑制PIM激酶可以使神经母细胞瘤对多克索鲁比产生敏感
Janet R Julson1, Colin H Quinn1, Nazia Nazam1
1Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Journal of pediatric surgery
|April 3, 2024
概括
抑制PIM激酶可以通过增加多克索鲁比吸收和与化疗协同来克服神经母细胞瘤化学抵抗. 这种方法对治疗高风险神经母细胞瘤充满希望.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 化学抵抗是高风险神经母细胞瘤复发的主要原因.
- 多种药物耐药性相关蛋白-1 (MRP1/ABCC1) 排泄有助于化学抵抗,并与神经母细胞瘤的不良结果有关.
- 在神经母细胞瘤中过度表达的PIM激酶,氨酸-氨酸激酶,是已知的MRP1.1的调节者.
研究的目的:
- 为了研究PIM激酶在神经母细胞瘤化学抵抗中的作用.
- 为了确定PIM激酶抑制是否可以通过调节MRP1.1,使神经母细胞细胞对化疗敏感.
- 评估PIM激酶抑制和 doxorubicin 在神经母细胞瘤细胞中的协同效应.
主要方法:
- 在神经母细胞瘤患者数据中对ABCC1,PIM1,PIM2和PIM3的基因表达分析.
- 治疗神经母细胞瘤细胞系 (SK-N-AS,SK-N-BE(2) 用多克索鲁比和泛PIM激酶抑制剂AZD1208.8.
- 通过流细胞计和细胞活性的细胞内多克索鲁比辛积累的评估,使用AlamarBlue测定.
主要成果:
- 在神经母细胞瘤中观察到PIM基因表达和ABCC1表达之间存在正相关性.
- 抑制PIM激酶导致细胞内多克索鲁比辛的积累增加,这表明MRP1.1的调节.
- 与AZD1208和多克索鲁比辛的联合治疗证明了对神经母细胞瘤细胞活力的协同效应.
结论:
- 通过对ABCC1.1的调节,PIM激酶可能在神经母细胞瘤的化疗耐药性中发挥作用.
- 抑制PIM激酶增强了细胞内多克索鲁比的积累,并与多克索鲁比在降低神经母细胞细胞活力方面表现出协同效应.
- 向PIM激酶是克服神经母细胞瘤化学抵抗的潜在治疗策略.
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