肺癌细胞对辐射的耐受性是影响肺癌放疗效果主要原因之一，STAT3参与了肿瘤细胞辐射耐受过程，放疗可诱导STAT3的磷酸化，增加Bcl-2的表达，后者诱发线粒体Cytochrome C的释放。miRNAs调节STAT3信号通路参与了肿瘤的发病过程，但未见其在肺癌细胞辐射耐受中的研究。 我们建立了移植肺癌细胞的小鼠模型，发现miRNAs能有效抑制辐射耐受肺腺癌细胞的增殖。在课题组研究miRNAs基础上，我们发现miR-93 能抑制肺腺癌细胞STAT3表达，而STAT3在辐射耐受肺腺癌细胞表达比对照细胞明显增高，提示STAT3及相关miRNAs可能参与了肺腺癌细胞辐射耐受过程。以此为出发点，本课题将重点研究miRNAs调节STAT3通路在肺腺癌细胞辐射耐受中的作用，探讨这些miRNAs对Bcl-2、线粒体相关Cytochrome C及Caspase因子等的影响，为肺腺癌放射治疗提供新靶点。

Radioresistance of lung cancer cells to radiation is one of the main obstacles to improve the effect of radiotherapy. STAT3-related pathway is involved in the process of tumor radioresistance to radiation. The phosphorylation of STAT3 induced by radiation, increases the expression of Bcl-2, which induced the release of mitochondrial Cytochrome C. STAT3 signal pathway regulated miRNAs were involved in the pathogenesis of tumors, but few studies focus on the roles of them in radioresistance of lung cancer. In recent study, we established a mouse model transplanted lung adenocarcinoma cells, and found that miRNA can effectively inhibit the proliferation of radioresistant lung adenocarcinoma cell. Based on the previous study of miRNAs, our results showed that miR-93 could inhibit expression of STAT3 and STAT3 was overexpressed in radioresistant lung adenocarcinoma cell compared with controls, suggesting that STAT3 and miRNAs may be involved in the process of lung cancer radioresistance. In this research, we will further study whether miRNAs were involved in reversing lung adenocarcinoma radioresistance by regualating STAT3 pathway,and investigate the effects of miRNAs on the expression of Bcl-2, Cytochrome C and Caspase factors to provide new targets for clinical treatment of lung adenocacinoma radioresistance.

肺癌细胞对辐射的耐受性是影响肺癌放疗效果主要原因之一，STAT3 参与了肿瘤细胞辐射耐受过程，放疗可诱导STAT3 的磷酸化，增加Bcl-2 的表达，后者诱发线粒体CytochromeC 的释放。miRNAs 调节STAT3 信号通路参与了肿瘤的发病过程，但未见其在肺癌细胞辐射耐受中的研究。在本课题研究中我们发现p-STAT3在辐射抵抗肺腺癌细胞株（A549/R）中表达明显增高，miR-320a等可调节A549/R细胞中STAT3和p-STAT3的表达。miR-320a及siRNA处理后，可诱导A549/R细胞发生凋亡，机理可能与调节STAT3、线粒体凋亡相关因子Caspase 3、Caspase 9等表达有关。本课题探讨这些miR-320a对STAT3、Bax、Bcl-2、Caspase 因子等的影响，为肺腺癌放射治疗提供新靶点。