高剂量的耐辐射肺癌细胞通过JAK2/p-STAT3/FASN通路储存了许多功能性脂质滴
Ting Yang1, Simiao Qiao1, Xiaoxia Zhu2
1Southern Medical University, No. 1023, South Shatai Road, Baiyun District, Guangzhou, 510515, Guangdong, China.
Journal of cancer research and clinical oncology
|August 8, 2023
概括
耐辐射的肺癌细胞通过内部合成和外部吸收积累脂质. 针对JAK2/p-STAT3/FASN通路可以通过减少脂质积累来提高放射治疗的有效性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 肺癌中的抗辐射能力仍然不太清楚.
- 脂质代谢越来越被认为是癌症进展和治疗耐药性的潜在因素.
研究的目的:
- 研究脂质代谢在肺癌中抗辐射机制中的作用.
- 确定潜在的治疗点,使肺癌对放射治疗产生敏感性.
主要方法:
- 使用油红色O染色方法量化脂质滴.
- 脂肪酸合成和运输中的关键蛋白质的西部斑分析.
- 通过Orlistat抑制新的脂肪酸合成.
- 脂肪酸合成酶 (FASN) 转录调节者的生物信息分析.
- 通过AZD-1480.0,抑制JAK2/STAT3通路的作用.
- 使用Chip-qPCR对转录因子结合的验证.
- 使用公共数据对FASN和LPL基因表达与患者预后的相关性分析.
主要成果:
- 与原始细胞相比,耐辐射肺癌细胞 (HDRR-LCC) 呈现出更多的脂质滴.
- HDRR-LCCs表现出对新脂肪酸合成和高细胞外脂肪酸吸收的偏好.
- 在HDRR-LCC中,FASN表达以辐射剂量依赖的方式增加.
- 抑制de novo脂肪酸合成 (奥利斯塔特) 和JAK2/STAT3通路 (AZD-1480) 减少了脂质滴,细胞增殖和辐射抵抗.
- 确定p-STAT3是FASN的上游调节者.
- 高FASN基因表达与接受放射治疗的肺癌患者的预后不佳相关.
结论:
- 抗辐射肺癌细胞中的脂质积累是由内源性脂肪酸合成和外源性脂质吸收驱动的.
- JAK2 / p-STAT3 / FASN信号通路是肺癌中脂质代谢和辐射抵抗的关键调节器.
- 针对JAK2 / p-STAT3 / FASN途径是一个有希望的策略,用于提高肺癌中放射治疗敏感度.
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