纳秒脉冲电场通过MAO-A促进肺癌细胞铁死亡用于肺癌精准消融

肺癌严重影响我国人民健康，亟待寻求新的局部消融技术来降低肺癌患者肿瘤负荷，改善肺癌患者的预后和生存质量。纳秒脉冲电场(nsPEF)以非热依赖的消融方式损毁肿瘤细胞，能消融肺癌且不损伤周围管道结构，但致死肺癌的机制未明。我们通过细胞实验发现肺癌细胞经nsPEF处理后出现铁死亡相关变化，且MAO-A水平升高；同时在临床肺癌病理样本中发现MAO-A的表达与肺癌的发生发展密切相关。本课题拟通过nsPEF处理不同肺癌细胞系及加入铁死亡抑制剂等实验明确nsPEF通过诱导肺癌细胞铁死亡的效应机制；通过逆转录病毒载体构建及CRISPR/Cas9敲除等技术揭示MAO-A为nsPEF诱导调控肺癌铁死亡的的分子靶点；通过体内动物实验验证nsPEF是适合肺癌局部消融需求的新疗法。结合自主研发的nsPEF发生器开展医工信电深度融合的系统研究，为肺癌的治疗提供新方案。

Lung cancer seriously affects the health of our people in China. It is urgent to seek new local ablation technology to reduce the tumor load of lung cancer patients and improve the prognosis and quality of life of lung cancer patients. Nanosecond pulsed electric field (nsPEF) destroys tumor cells in a heat independent manner. It can ablate lung cancer without damaging the surrounding pipeline structure. However, the mechanism of nsPEF-induced lung cancer cell death remains unclear. We found that lung cancer cells treated with nsPEF showed ferroptosis related changes, and the level of MAO-A increased. At the same time, it was found that the expression of MAO-A is closely related to the development of lung cancer. In this project, we intend to clarify the mechanism of nsPEF in inducing ferroptosis of lung cancer cells by treating different lung cancer cell lines with nsPEF and adding ferroptosis inhibitor;to reveal that MAO-A is the molecular target of nsPEF in inducing ferroptosis of lung cancer by constructing retroviral vector and CRISPR / cas9 knockout technology; to verify that nsPEF is a new therapy for local ablation of lung cancer by animal experiments in vivo. Combined with the self-developed nsPEF generator, the system research of deep integration of medical information and electricity will be carried out, which will provide a new scheme for the treatment of lung cancer.