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共同准FASN和mTOR抑制了卵巢黑色素瘤的生长

Anna Han^1,2, Dzmitry Mukha³, Vivian Chua¹

¹Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.

|July 14, 2023

概括

向脂肪酸合成酶 (FASN) 和哺乳动物向拉巴胺素 (mTOR) 显示出膜黑色素瘤 (UM) 治疗的前景. 通过阻止细胞循环和新陈代谢,抑制FASN和mTOR都显著减少了UM细胞的生长.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
代谢研究研究代谢研究

背景情况:

卵巢黑色素瘤 (UM) 经常转移,有效治疗方法有限.
代谢重编程是癌症的标志,提供潜在的治疗点.
GNAQ (Q209L) 突变驱动UM的发展,并与改变的细胞代谢有关.

研究的目的:

为了识别皮膜黑色素瘤中独特的代谢脆弱性.
研究脂肪酸合成酶 (FASN) 在UM细胞生长中的作用.
评估向FASN和哺乳动物向拉巴胺素 (mTOR) 信号传导在UM中的治疗潜力.

主要方法:

建立了一个正常的冠状腺黑色细胞 (NCM) 线,用GNAQ (Q209L) 转化为UM模型.
评估脂肪酸合成酶 (FASN) 表达及其与UM细胞mTOR和SREBP1水平的相关性.
利用FASN和mTOR抑制剂,单独和同时,以评估它们对UM细胞增殖,细胞周期和代谢途径的影响.

主要成果:

与NCM相比,UM细胞表现出高FASN表达,与增加的mTOR激活和SREBP1.1相关.
单剂FASN或mTOR抑制降低了UM细胞的生长.
同时抑制FASN和mTOR通过诱导细胞循环停止和抑制关键代谢途径,包括葡萄糖利用和脂肪酸生物合成,显著抑制UM细胞增殖.

结论:

脂肪酸合成酶 (FASN) 在皮膜黑色素瘤细胞的生长和存活中发挥着关键作用.
联合抑制FASN和mTOR信号传递代表了转移性UM的有前途的治疗策略.
准脂质代谢为开发UM的新疗法提供了一种可行的方法.

关键词:

这是GNAQQ.脂肪酸合成酶是一种脂肪酸.在 mTOR 路径上.代谢抑制的代谢抑制阴膜性黑色素瘤是什么

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