OPN/IRF1/HOTAIR通路对125I 粒子放射生物效应的作用及分子机制

To reduce radiation resistance and improve radiobiological effect is a difficult problem of 125I seeds for the treatment of solid tumors. We have proven that the expression of OPN in progressive tumors increases after irradiation of 125I seeds and it can decrease the radiobiological effect. Then what is the pathway of OPN in the downregulation of 125I seeds’ radiobiological effect? Our previous study has been clear that HOTAIR can promote the invasion and migration of tumor cells. We also find that OPN can stimulate the expression of HOTAIR by reducing the inhibition of IRF1 on HOTAIR (Biochim Biophys Acta.2014). Further pre-experiment showed that the expression of HOTAIR in progressive tumors increased significantly after irradiation of 125I seeds and there was a positive correlation between the expression of HOTAIR and OPN. Then we first propose the pathway of OPN/IRF1/HOTAIR by which OPN can realize the regulation of 125I seeds’ radiobiological effect. To obtain the reliable evidence of this pathway in the involvement and regulation of 125I seeds’ radiobiological effect, we’ll use the methods of MTT, transwell, FCM, etc. We will also illuminate the the related molecular mechanisms of action at different level of this pathway. So more sufficient basis will be provided to help us find new targets to improve the radiobiological effect on tumor cells and clinical effect of 125I seeds.

降低放射抵抗、提高放射生物效应是125I粒子治疗实体瘤的难题。我们已证实125I粒子照射后肿瘤进展组织中OPN的表达升高，并证明OPN可降低放射生物效应。那么OPN下调粒子放射生物效应的通路是什么？我们前期研究明确了HOTAIR可促进肿瘤细胞的侵袭、迁移，而OPN可通过降低IRF1对HOTAIR的抑制来刺激HOTAIR的表达 (Biochim Biophys Acta.2014)。进一步预实验显示：粒子照射后肿瘤进展组织中HOTAIR的表达升高且与OPN呈正相关。由此我们提出OPN下调125I粒子放射生物效应的通路，即可通过OPN/IRF1/HOTAIR来实现其调控作用。本项目拟采用MTT、细胞迁移及流式细胞术等方法，旨在获得这一通路参与调控粒子放射生物效应的可靠证据。我们将阐明通路中各个环节作用的分子机制，为寻求提高125I粒子对肿瘤放射生物效应的新靶点、进一步提高临床疗效提供科学依据。

降低放射抵抗、提高放射生物效应是125I粒子治疗实体瘤的难题。我们证实125I粒子照射后肿瘤进展组织中OPN的表达升高，并证明OPN可降低放射生物效应。那么OPN下调粒子放射生物效应的通路是什么目前仍不清楚。我们研究明确了HOTAIR可促进肿瘤细胞的侵袭、迁移，而OPN可通过降低IRF1对HOTAIR的抑制来刺激HOTAIR的表达 。进一步预实验显示：粒子照射后肿瘤进展组织中HOTAIR的表达升高且与OPN呈正相关。由此我们提出OPN下调125I粒子放射生物效应的通路，即可通过OPN/IRF1/HOTAIR来实现其调控作用。本项目采用MTT、细胞迁移及流式细胞术等方法，旨在获得这一通路参与调控粒子放射生物效应的可靠证据。我们将阐明通路中各个环节作用的分子机制，为寻求提高125I粒子对肿瘤放射生物效应的新靶点、进一步提高临床疗效提供科学依据。