早熟衰老是放疗杀伤肿瘤细胞的方式之一，诱导肿瘤细胞早衰作为新的肿瘤治疗策略具有广阔的研究前景，但其相关机理尚不明确。本课题组发现辐射在杀伤肿瘤细胞的同时，还会激活细胞内STAT3从而对抗辐射的杀伤效应，并促进肿瘤转移。在前期国家自然基金的资助下，我们发现受辐射调控的STAT3表达抑制不但阻断辐射诱导的肿瘤细胞转移，抑制细胞增殖，还增加肿瘤细胞早衰的比例，促进调节早衰的caveolin-1的表达。提示辐射诱导的STAT3活化可能通过caveolin-1抑制了部分细胞早衰的发生，从而增强细胞的辐射抗性。本项目将采用EMSA等方法，体内外水平探索 caveolin-1及下游衰老通路Sirt1/p53在STAT3抑制辐射诱导细胞早衰中的作用机制。本项目的完成可在理论上阐明STAT3调控caveolin-1介导的抗早衰在肿瘤细胞辐射抗性中的作用及其机制，为临床肿瘤放疗寻找潜在的治疗靶点提供实验依据。

Induction of premature cell senescence is one of manners of radiation-induced cancer cells death, which has been considered as a novel strategy for cancer therapy and a broad scope in future. However, the mechanisms involved in premature cell senescence are still unclear. Our previous study found that ionizing radiation could activated the signal transducer and activator of transcription 3 (STAT3) in cancer cells, which subsequently attenuated the cell killing effect of radiation to a certain extent and promoted the tumor metastasis, although many of th e tumor cells did be killed by radiation. Under the support of National Science Foundation of China, our preliminary study showed that the functional suppression of STAT3 not only blocked the tumor cell metastasis induced by radiation but also increased the proportion of premature cell senescence in tumor cells. Furthermore, the expression of caveolin-1 involved in the regulation of premature cell senescence increases after ration. These results implied that the activation of STAT3 induced by radiation might partly inhibit the occurrence of premature cell senescence via caveolin-1, which might contribute to the increase in the radioresistance of cancer cells. Based on our previous results of study, the current study will investigate the role caveolin-1 and its downstream pathway, caveolin-1/Sirt1/p53, in STAT3-suppressed premature cell senescence induced by radiation using various methods such as EMSA and CHIP. This study hopes to explore the role of premature cell senescence resistance mediated by STAT3-regulated caveolin-1 and its mechanisms in theory, and provide the experiment evidence for the screen of potential therapeutic targets.