PLK1通过酸路径/铁化调节食道状细胞癌的化学辐射疗法敏感性
Mengnan Zhao1, Tao Lu2, Guoshu Bi1
1Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
|October 25, 2023
概括
在食道状细胞癌 (ESCC) 中降低调节的波罗样激酶1 (PLK1) 促进铁,增强对化学放射治疗的敏感性. 这表明PLK1是ESCC治疗的潜在治疗点.
科学领域:
- 在瘤学瘤学.
- 细胞死亡机制 细胞死亡机制
- 分子生物学分子生物学
背景情况:
- 食道状细胞癌 (ESCC) 是中国流行的一种癌症,通常在晚期被诊断出来.
- 新的辅助疗法对先进的ESCC至关重要,需要确定新的治疗点.
- 铁,一种依赖于铁的编程细胞死亡,越来越多地被认为是癌症发展中的作用.
研究的目的:
- 调查Polo像激酶1 (PLK1) 在ESCC对化疗辐射疗法的敏感性中的作用.
- 探索涉及铁和酸通路 (PPP) 的潜在机制.
主要方法:
- 在ESCC细胞系 (KYSE150,ECA109) 中使用CRISPR/Cas9.9敲除了PLK1.
- 评估了对G6PD,NADPH,GSH,脂质过氧化和线粒体形态学的影响.
- 通过CCK-8和克隆形成试验评估了对放射治疗,帕克利塔塞尔和西斯普拉丁的敏感性.
- 研究了裸体小鼠的瘤发生和YY1转录因子调节.
- 在患者队列 (GEO数据库和临床中心) 中分析PLK1和YY1表达和相关性.
主要成果:
- PLK1淘汰赛降低了G6PD,NADPH和GSH,增加了脂质过氧化和促进铁亡.
- 缺乏PLK1的细胞表现出对电离辐射,帕克利塔塞尔和西斯普拉丁的增强敏感性,并诱导铁亡.
- 外源性GSH逆转了PLK1淘汰对铁和化学放射治疗敏感性的影响.
- 转录因子YY1积极调节了PLK1的表达,在ESCC患者中,这两者都有积极的相关性.
- 高PLK1表达与较差的患者存活率相关.
结论:
- 下调PLK1抑制酸通路 (PPP),降低NADPH和GSH,促进铁亡,并使ESCC对化学放射治疗敏感.
- 转录因子YY1积极调节PLK1,它们的共同表达与预后有关.
- PLK1作为一种潜在的预测生物标志物和治疗点,可以提高ESCC化学放射治疗的敏感性.
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