LCN2影响肿瘤细胞辐射耐受性的分子机制研究

Radio-resistance is a major challenge in tumor radiotherapy. Enhanced understanding of the mechanisms involved in the tumor cell radio-resistance would be helpful for developing novel therapeutic strategies and improving patients’ response to therapy. In our previous study in ATM gene knockout (ATM-/-) cells and/or radio-resistant tumor cells established in our lab, we found that LCN2 is a radio-resistance associated gene and may play critical roles in ATM-mediated tumor cell radio-sensitivity alteration following radiation treatment. In this project, we will investigate the effects of LCN2 on tumor cell radio-sensitivity, clarify the roles of LCN2 in the occurrence of tumor cell radio-resistance both in vitro and in vivo, and reveal the molecular mechanisms involved in this progression. Furthermore, we will find out how the LCN2 gene is up-regulated in radio-resistant tumor cells, and evaluate its significance in clinical radiotherapy. The findings of this study will provide novel targets for tumor radiotherapy.

细胞对辐射耐受是肿瘤放射治疗中面临的一大挑战。增进对肿瘤细胞辐射耐受分子作用机制的认识，有助于开发肿瘤放疗新策略，提高癌症患者的放疗效果。在本实验室前期构建的ATM基因敲除(ATM-/-)和辐射耐受的肿瘤细胞中，我们发现LCN2是一个肿瘤细胞辐射耐受相关基因，在ATM调控的肿瘤细胞辐射敏感性变化中起着重要的作用。本项目将在细胞和动物水平上研究LCN2对肿瘤细胞辐射敏感性的影响，搞清楚它在肿瘤细胞辐射耐受性产生中的作用，并通过分子和细胞生物学手段揭示LCN2调控肿瘤细胞辐射耐受性的作用机制。进一步地，我们还将阐明辐射耐受肿瘤细胞中LCN2表达上调的原因，评估其在肿瘤放疗中的临床意义。本项目研究成果将为开发更加有效的肿瘤放疗策略提供新靶点。

增进对肿瘤细胞辐射耐受分子作用机制的认识，有助于开发肿瘤放疗新策略，提高癌症患者的放疗效果。在本项目研究中，我们发现脂质运载蛋白2（LCN2）编码基因LCN2是一个肿瘤细胞辐射耐受相关基因，在ATM调控的肿瘤细胞辐射敏感性变化中起着重要的作用。分子和细胞生物学实验揭示LCN2促进肿瘤细胞辐射耐受性主要是通过调节肿瘤细胞生长和转移相关途径。进一步地，我们还发现在辐射耐受肿瘤细胞中ATM-NFκB信号通路对LCN2基因表达发挥了重要的调控作用。最后，本项目研究提示LCN2可作为提高肿瘤放疗效果潜在的新靶点。