肺癌患者中接近一半的病人患有抑郁症，而抑郁导致癌症死亡率增加。但目前还缺乏明确的分子机制研究来解释。在前期的细胞实验中，已证实通过调节β2-ADR/cAMP/PKA信号通路能抑制肺癌细胞的增殖。并且，我们已成功建立慢性社会挫败应激-肺癌动物模型，并初步证实慢性应激在肺癌细胞增殖、浸润及转移中起重要作用。此外，慢性应激促进肺肿瘤的增殖时，β2-ADR/cAMP/PKA信号通路的表达水平显著地增加。基于前期研究结果，本课题项目中我们将阐明β2-ADR在慢性应激促进肺癌进展中的作用，并通过调节β2-ADR观察是否可有效阻断慢性应激对肺癌进展的影响。利用基因测序筛选β2-ADR信号通路的作用靶点基因，重点阐明β2-ADR/cAMP/PKA信号通路作用机制。我们将进一步进行人体实验，探索肺癌患者的个体化差异相关基因，阐明β2-ADR/cAMP/PKA信号通路的作用机制。

Many cancer patients have a disorder with depression, which leads to increased the cancer mortality, but the molecular mechanism of this process is still unclear. In the previous cell experiments, we confirmed that the proliferation of lung cancer cells could be decreased by the inhibition of β2-ADR/cAMP/PKA signaling pathway. In addition, we successfully established an animal model of chronic social defeat stress-lung cancer, and preliminarily confirmed that chronic stress plays an important role in the proliferation, invasion and metastasis of lung cancer cells. Moreover, the expression levels of β2-ADR/cAMP/PKA signaling pathway were increased in lung tumors proliferation induced by chronic stress. In this study, we will explain the role of β2-ADR in promoting lung cancer progression by chronic stress, and observe whether the effect of chronic stress on lung cancer progression can be effectively blocked by regulating β2-ADR. We also plan to screen the target genes of the β2-ADR signaling pathway, and clarify an action mechanism of the β2-ADR/cAMP/PKA signaling pathway. We will conduct further human experiments to explore the individual difference of target genes in lung cancer patients, and elucidate an action mechanism of the β2-ADR /cAMP/PKA signaling pathway.