胃癌是一种与中枢神经系统活动密切相关的疾病。由于生活不规律，工作压力大，过度饮酒等带来的长期应激状态会引起脑内多种神经递质代谢异常进而引发慢性胃炎，胃溃疡等胃癌发生的重要危险因素。研究表明β-交感肾上腺素系统的长期过度激活将显著降低人体固有免疫反应中自然杀伤细胞（NK）的数量和活性，导致肿瘤发生发展。而β-肾上腺素受体抑制剂普萘洛尔可以逆转由于应激引起的NK细胞数量的减少以及功能的失活。同时，我们的前期研究显示普萘洛尔可以通过抑制AKT/MAPK信号通路的磷酸化杀伤肿瘤细胞。因此我们提出假说，普萘洛尔将可能通过激活机体固有免疫以及直接杀伤肿瘤的双重机制达到阻滞胃癌发生发展的作用。本项目拟运用免疫印迹，免疫组化，转录组测序等方法，从细胞、小鼠和临床病例三个研究层面，系统阐述普萘洛尔在胃癌发生发展过程双重抗癌作用的分子机制。本项目的开展将为胃癌的预防与临床治疗提供新的思路与理论支持。

Gastric cancer is one kind of disease correlated closely with the activity of central nervous system. The long-term activation state resulting from irregular life style, strong work stress and overdrinking could lead to a variety of brain neurotransmitter metabolic abnormalities and then bring about chronic gastritis or gastric ulcer which is the key risk factor of gastric carcinogenesis. Researches have showed that the long-term over activation of β- sympathetic adrenaline system would significantly reduce the number and activity of natural killer (NK) cells in human innate immune response, resulting in the occurrence and development of tumor. However, β-adrenergic receptor blockade propranolol could reverse the reduction of NK cell number and inactivation of function. Meanwhile, our preliminary study has shown that propranolol could kill tumor cells through suppressing the phosphorylation of AKT/MAPK pathway. Therefore, we put forward the hypothesis that propranolol could suppress the occurrence and development of gastric cancer through the mechanism of both activating the innate immunity and directly killing tumor cells. This project has planned to systematically elaborate the dual-anticancer molecular mechanism of propranolol in the process of gastric cancer genesis and development from the level of cell, mice and clinical cases using the method of western blot, immunohistochemistry, transcriptome Sequencing, etc. The development of this project would provide new thought and theoretic support for the prevention and clinical treatment of gastric cancer.