CLIN CANCER RES:过表达的脂肪酸合成酶影响伊马替尼治疗胃肠道间质瘤疗效

2017-08-29 MedSci MedSci原创

对于胃肠道间质瘤(GIST)尚缺乏脂质代谢酶的研究,包括脂肪酸合成酶(FASN)。CLIN CANCER RES近期发表了一篇文章, 研究脂肪酸合成酶在胃肠道间质瘤中扮演的角色。

对于胃肠道间质瘤(GIST)尚缺乏脂质代谢酶的研究,包括脂肪酸合成酶(FASN)。CLIN CANCER RES近期发表了一篇文章, 研究脂肪酸合成酶在胃肠道间质瘤中扮演的角色。

350例胃肠道间质瘤标本中可检测到脂肪酸合成酶免疫表达,包括213例已知KIT/PDGFRA/BRAF亚型。在伊马替尼抵抗脂肪酸合成酶过表达的GIST细胞中,作者通过RNAi分析过表达的脂肪酸合成酶以及FASN靶向的C75在肿瘤亚型、凋亡、自噬、KIT转录,PI3K/AKT/mTOR活化和伊马替尼抵抗中起到的作用。在体内实验中评估双重阻滞FASN和KIT的治疗效果。研究结果表明,随着根据NCCN指南判断的风险升高,FASN mRNA显着增加。FASN过表达与非胃部间质瘤,不良亚型,风险水平增加有关并可以独立预测较短的无病生存期。在体外实验中,敲除FASN抑制细胞增殖和转移,降低PI3K/AKT/mTOR通路活性,改善GIST细胞伊马替尼抵抗情况。C75转录抑制KIT启动子,下调KIT表达和磷酸化,减弱PI3K/AKT/mTOR/RPS6/4E-BP1通路活性,与伊马替尼表现出剂量依赖治疗效果。与两种单抗治疗相比,C75/伊马替尼联合能够更有效地抑制异种移植模型的肿瘤生长,表现出KIT磷酸化减弱,Ki-67,磷酸化PI3K/AKT/mTOR水平降低。

文章最后认为,该研究阐明了过表达的FASN在胃肠道间质瘤中起到的预后、生物学以及治疗作用。C75抑制KIT转录活性,阻滞PI3K/AKT/mTOR活化,为治疗伊马替尼抵抗胃肠道间质瘤时双重阻滞KIT和FASN提供了证据。

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    2018-04-03 lq1767
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    2017-08-30 luominglian113

    学习了.谢谢分享

    0

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