佛醇调节p62 / Keap1 / Nrf2信号通路,以诱导骨髓瘤细胞中的铁亡
Xiangchen Zeng1, Guang-Xun Lin1, Xianhui Zeng2
1Department of Orthopedic Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361001, China; School of Medicine, Xiamen University, Xiamen 361102, China.
概括
抗精神病药物Penfluridol通过抑制癌细胞的生长和迁移,在治疗骨髓瘤 (OS) 中表现有前途. 它诱导铁亡,细胞死亡途径,为这种具有挑战性的癌症提供了一种新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 细胞生物学 细胞生物学
背景情况:
- 骨髓瘤 (OS) 治愈率已经稳定,需要新的治疗方法.
- 抗精神病药物Penfluridol已经证明对其他癌症有效,但其在OS中的作用尚未被探索.
研究的目的:
- 为了研究penfluridol的抗骨肉瘤作用.
- 阐明夫醇在OS细胞中的作用背后的分子机制.
主要方法:
- 进行了细胞增殖,迁移和细胞周期检测.
- 使用RNA测序 (RNA-Seq) 和西方斑点分析.
- 使用异种移植瘤模型进行了体内研究.
主要成果:
- 利醇抑制了OS细胞的增殖和迁移,诱导G2/M阶段停止.
- 利醇通过促进Fe2+和脂质过氧化,同时降低GSH,增加了活性氧物种 (ROS) 和诱导铁亡.
- 这涉及p62/Keap1/Nrf2通路,p62的过度表达逆转了铁亡.
结论:
- 弗利多尔在体外和体内都表现出显著的抗骨髓瘤活性.
- 由p62/Keap1/Nrf2通路介导的Penfluridol诱导的铁,是其抗癌作用的关键机制.
- 利醇是骨髓瘤治疗的潜在治疗剂.
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