SLC7A11介导的铁死亡调控对口腔白斑病光动力治疗的增效作用及其分子机制研究

光动力治疗在口腔白斑病(OLK)的管理中展示了独特的优势，但不同个体显示的疗效异质性亟待克服。铁死亡是细胞命运领域的研究热点（Cell,2019）。申请人前期发现铁死亡调控关键因子SLC7A11可能参与OLK的发生发展，但是否可以成为OLK光动力治疗的增效靶点，尚待进一步证实。为此，拟开展以下研究：①临床样本探寻SLC7A11信号通路分子在OLK发生发展中的动态变化及其对光动力治疗疗效的影响；②细胞模型进一步证实干预SLC7A11信号通路对OLK角质形成细胞命运的影响；③细胞模型探索干预SLC7A11信号通路对OLK光动力治疗的增效作用及可能的机制；④动物模型验证干预SLC7A11信号通路对OLK进程的影响以及对OLK光动力治疗的增效作用及分子机制。结果不仅有助于阐明OLK的发病机制，而且有助于提高OLK光动力治疗的效率，为个体化靶向防治OLK及其他口腔黏膜潜在恶性疾患提供依据。

Photodynamic therapy (PDT) has great potential in the treatment of oral leukoplakia (OLK), but further studies are needed to improve its effect and efficiency. Ferroptosis is the hotspot of the cell growth and death research. Previous studies of our group showed that key regulator of ferroptosis, SLC7A11 and its signaling molecules might play an important role in the development of OLK, and might be a potential target to improve PDT performance in OLK treatment. The following studies are designed to prove that hypothesis:①Expression pattern of SLC7A11 and its signaling molecules in different stages of OLK sample and the relationship between expression of these proteins and risk of cancer development in OLK, as well as the effect and efficiency of PDT;②In vitro validation of the influence of interfering SCL7A11 signaling on the fate of OLK keratinocytes; ③In vitro exploration of the influence and potential mechanisms of interfering SCL7A11 signaling on the response of OLK keratinocytes to PDT treatment;④In vivo validation of the influence of interfering SCL7A11 signaling on the development of OLK and the response of OLK lesion to PDT treatment. The results of this research will help with the understanding of the molecular mechanisms of OLK progeression, improve the efficiency of PDT treatment of OLK. and facilitate the development of individualized treatment strategy for OLK and other oral potentially malignant disorders.