间充质干细胞来源的外泌体通过Stat3通路的辐射增敏机理研究

Radiotherapy is an important strategy in achieving the efficient control of tumor. However, radio-resistance of tumor cells limits the curable potential and contributes to local recurrences. Discovery for mechanisms of tumor radiosensitivity and methods of sensitizing tumor to radiation will be extremely important for improvement of radiotherapy. In recent years, more and more studies have focused on the effects of exosomes derived from mesenchymal stem cells (MSCs) on tumors which is a hot topic at present. In previous studies, we found that MSCs derived exosomes can enhance radiosensitivity of breast cancer cells, by means of suppression on the phosphorylation of Stat3, but the mechanism was unclear. On this basis, we made a further research to study whether it were exosomes that played an important role on radiosensitizing effect. To test this hypothesis, we used real-time imaging system to investigate the effect of MSCs-exosomes on aggressive breast cancer cells in vitro and in vivo. We specifically discovered that MSCs-exosomes sufficiently suppressed Stat3 signaling pathway activation in tumor cells leading to a reduction in tumorigenesis and an enhancement in radiosensitivity. It is expected to provide further evidence for MSCs-exosomes acting as a new anti-cancer drug. Indeed, the execution of this study will present great value in both basis research and clinical application of MSCs-exosomes in tumor radiotherapy.

肿瘤的辐射耐受降低了放疗疗效，怎样增强辐射敏感性并明确其机制是放射医学急需解决的课题之一。越来越多的研究致力于探讨间充质干细胞来源的外泌体对肿瘤的影响，并已成为研究热点。Stat3在多种肿瘤中高表达，其活化水平与肿瘤生长、转移及预后密切相关。我们在前期研究中发现间充质干细胞外泌体可抑制乳腺癌生长、增强细胞辐射敏感性。但其作用机理尚不明确，在此基础上，我们假设：外泌体通过抑制Stat3通路调节乳腺癌辐射敏感性。本研究将：从细胞和动物水平探讨外泌体对乳腺癌的辐射增敏作用；Stat3通路与辐射敏感性的关系；研究外泌体是否通过抑制Stat3通路来调节辐射敏感性；通过全转录组测序技术筛选外泌体中抑制Stat3通路，增强辐射敏感性的关键分子。本课题将为外泌体通过辐射增敏治疗肿瘤的临床研究提供理论依据和新的肿瘤治疗靶点。

肿瘤的辐射耐受降低了放疗疗效，怎样增强辐射敏感性并明确其机制是放射医学急需解决的课题之一。越来越多的研究致力于探讨间充质干细胞来源的外泌体对肿瘤的影响，并已成为研究热点。Stat3在多种肿瘤中高表达，其活化水平与肿瘤生长、转移及预后密切相关。我们在前期研究中发现间充质干细胞外泌体可抑制乳腺癌生长、增强细胞辐射敏感性。但其作用机理尚不明确，在此基础上，我们验证了泌体通过抑制Stat3通路调节乳腺癌辐射敏感性。结果表明：外泌体联合放射，抑制了肿瘤的增殖，促进细胞凋亡，阻滞细胞周期；并且抑制了肿瘤细胞自我更新和血管新生的能力。本研究将为外泌体通过辐射增敏治疗肿瘤的临床研究提供理论依据和新的肿瘤治疗靶点。