Lung cancer is a leading cause of cancer death worldwide, with high incidence and poor survival rates. Cold atmospheric plasma (CAP) technology has emerged as a promising therapeutic approach for cancer treatment, inducing oxidative stress in malignant tissues without causing thermal damage. However, the role of CAP in regulating lung cancer cell ferroptosis remains unclear. Here, we observed that CAP effectively suppressed the growth and migration abilities of lung cancer cells, with significantly increased ferroptotic cell death, lipid peroxidation, and decreased mitochondrial membrane potential. Mechanistically, CAP regulates SLC7A11-mediated cell ferroptosis by modulating HOXB9. SLC7A11, a potent ferroptosis suppressor, was markedly reduced by HOXB9 knockdown, while it was enhanced by overexpressing HOXB9. The luciferase and ChIP assays confirmed that HOXB9 can directly target SLC7A11 and regulate its gene transcription. Additionally, CAP enhanced the acetylation modification level of HOXB9 by promoting its interaction with acetyltransferase p300/CBP-associated factor (PCAF). Acetylated HOXB9 affects its protein ubiquitination modification level, which in turn affects its protein stability. Notably, the upregulation of SLC7A11 and HOXB9 mitigated the suppressive effects of CAP on ferroptosis status, cell proliferation, invasion, and migration in lung cancer cells. Furthermore, animal models have also confirmed that CAP can inhibit the progression of lung cancer in vivo. Overall, this study highlights the significance of the downregulation of the HOXB9/SLC7A11 axis by CAP treatment in inhibiting lung cancer, offering novel insights into the potential mechanisms and therapeutic strategies of CAP for lung cancer.

中文翻译：

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冷大气等离子体通过调节 PCAF 介导的 HOXB9 乙酰化增强非小细胞肺癌中 SLC7A11 介导的铁死亡


肺癌是全球癌症死亡的主要原因，发病率高，生存率低。冷大气等离子体（CAP）技术已成为一种有前景的癌症治疗方法，可在恶性组织中诱导氧化应激而不引起热损伤。然而，CAP在调节肺癌细胞铁死亡中的作用仍不清楚。在这里，我们观察到 CAP 有效抑制肺癌细胞的生长和迁移能力，显着增加铁死亡细胞死亡、脂质过氧化和线粒体膜电位降低。从机制上来说，CAP 通过调节 HOXB9 来调节 SLC7A11 介导的细胞铁死亡。 SLC7A11 是一种有效的铁死亡抑制剂，HOXB9 敲低可显着降低 SLC7A11 的水平，而过表达 HOXB9 则可显着增强 SLC7A11 的水平。荧光素酶和 ChIP 检测证实 HOXB9 可以直接靶向 SLC7A11 并调节其基因转录。此外，CAP 通过促进 HOXB9 与乙酰转移酶 p300/CBP 相关因子 (PCAF) 的相互作用来增强 HOXB9 的乙酰化修饰水平。乙酰化HOXB9影响其蛋白质泛素化修饰水平，进而影响其蛋白质稳定性。值得注意的是，SLC7A11 和 HOXB9 的上调减轻了 CAP 对肺癌细胞铁死亡状态、细胞增殖、侵袭和迁移的抑制作用。此外，动物模型也证实CAP在体内可以抑制肺癌的进展。总体而言，本研究强调了 CAP 治疗下调 HOXB9/SLC7A11 轴在抑制肺癌中的重要性，为 CAP 治疗肺癌的潜在机制和治疗策略提供了新的见解。