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catalase作为转移性割抵抗性前列腺癌的新型药物标

Frantzeska Giginis¹, Joshua Wang¹, Aaron Chavez¹

¹Department of Cell, Molecular and Systems Biology, University of California Riverside, CA, USA.

American journal of cancer research

|July 10, 2023

概括

降低降解氧化压力的酶catalase,可能为转移性割耐性前列腺癌 (mCRPC) 提供一种新的治疗策略. 降低前列腺癌细胞中的催化酶水平,损害了小鼠的瘤生长和血管化.

科学领域:

在瘤学瘤学.
生物化学生物化学
分子生物学分子生物学

背景情况:

前列腺癌 (PCa) 是一种常见的恶性瘤,通常用抗雄激素缺乏疗法 (ADT) 治疗.
对转移性割抵抗性前列腺癌 (mCRPC) 的ADT是无效的,需要新的治疗方法.
氧化应激 (OS) 在癌症进展中起作用,而催化酶是控制OS水平的关键酶.

研究的目的:

为了研究catalase在mCRPC的进展中的作用.
为了确定调节催化酶水平是否影响mCRPC细胞行为和瘤发育.

主要方法:

利用CRISPR尼克酶系统在PC3mCRPC细胞系中创建一个催化酶倒置 (Cat+/-).
评估细胞表型,包括H2O2敏感性,迁移,附着和增殖.
采用SCID小鼠异种移植模型来评估瘤的形成和特征.
通过重新引入功能性催化酶进行了救援实验.

主要成果:

猫+/-细胞对H2O2的敏感性增加,迁移减少,原附着性差,Matrigel附着性高,增殖速度较慢.
与野生类型相比,来自Cat+/-细胞的异体移植形成了较小的瘤,原蛋白减少,缺乏血管化.
救援实验证实,恢复催化酶功能可以逆转这些观察到的表型.

结论:

酶在阻止mCRPC的发展和进展方面发挥着关键作用.
调节酶活性为mCRPC治疗提供了一个潜在的新疗法标.
向催化酶可以利用前列腺癌细胞对氧化应激的敏感性.

关键词:

雄激素受体的受体雄激素受体克里斯普尔是什么意思?克里斯普尔是什么意思?药物耐药性耐药性药物耐药性转移转移转移转移氧化应激是一种氧化应激.

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