流行病学研究提示良性精神情绪对肿瘤的防控具有积极意义，但长期以来缺乏实验证据支持。丰富生存环境（Enriched environment, EE）是公认的能够诱导动物产生良性心理应激的模型。最新研究表明，EE对小鼠恶性肿瘤具有广泛的抑制作用。本项目将在以往现象观察的基础上，首次探讨EE抑瘤的细胞内分子机制。根据课题组前期多组学结果发现的EE对癌细胞线粒体蛋白具有普遍下调作用的线索，我们将进一步探讨：1.EE对肿瘤线粒体形态、结构和能量代谢的影响；2.以小鼠胰腺癌模型为重点，通过一系列体内外实验，确认受EE调控最为显著的线粒体呼吸相关基因Uqcrc1为一新的胰腺癌相关基因；3.证实EE通过干扰Uqcrc1及线粒体呼吸功能发挥抑瘤作用。本研究首次从细胞能量代谢的角度，探索EE及其所诱导的良性心理反应在抗癌中的作用机制，为在肿瘤治疗和康复中倡导生物-心理-社会医学模式提供实验依据。

Epidemiology studies have suggested that psychological factors are associated with cancer development. However, there is few experimental evidence to support this conclusion. Enriched environment (EE) is a well-established animal model which confers benign psychological stress to the host. Recently, increasing evidence has show that EE demonstrates a broad spectrum of anti-tumor effects. We have reported before that EE Inhibited mouse pancreatic cancer growth and down-regulated the expression of mitochondria-related genes in cancer cells. Based on these findings, in the current study, we will focus on the intracellular mechanism by which EE suppresses tumor cell growth. We will first investigate whether EE influences metabolic function of mitochondria by down-regulating the genes involved in tricarboxylic acid cycle an oxidative phosphorylation in a variety of subcutaneous tumor models including pancreatic cancer, colon cancer, lung cancer, etc. Then, we will prove that Uqcrc1 gene, a mitochondrial protein coding gene whose expression level is significantly regulated by EE condition, is a novel pancreatic cancer-related gene. Lastly, we will provide both in vitro and in vivo evidence to show that EE exerts the anti-tumor effect by targeting Uqcrc1 and its associated mitochondrial energy metabolism. This study is the first to explore the mechanism underlying the inhibitory effect of EE on cancer cell growth through the direction of cellular energetics. The results from this project may provide experimental evidence for advocating bio-psycho-social medical models in cancer prevention and treatment.