BACKGROUND AND PURPOSE Patients with life-threatening illnesses, such as cancer, experience emotional distress. This study was to investigate the molecular and cellular mechanisms of relevant psychological stressor on tumor growth and therapeutic resistance. MATERIALS AND METHODS Stress was induced in C57BL/6J mice bearing LLC lung tumors by exposure to a conspecific mice receiving inescapable foot shocks. Mice were irradiated at 7 Gy for 3 consecutive days. Behaviors were monitored by open field test (OFT), elevated plus maze (EPM), sucrose preference test (SPT), and learned helplessness (LH) test. Protein expression in tissues and cultured cells were measured by Western blot. RESULTS This study in animals showed that observing a conspecific mouse receiving foot shocks induced depression like behaviors with increased plasma corticosterone and adrenaline levels which increased tumor growth and radioresistance. Stress increased Wnt1, Drosha, and vimentin expression and decreased E-cadherin expression in tumor tissues. The combination of stress and irradiation enhanced radioresistance along with the increase in vimentin expression. The in vitro study showed that a β2-adrenergic receptor (β2-AR) agonist blocked irradiation-induced cell apoptosis and decreased cell viability, while silencing β2-AR expression reduced the protective effects of β2-AR agonist. β2-AR agonist obviously increased Wnt1 and Drosha expression in LLC-1 cells. CONCLUSION Psychological stress increased tumor growth and enhanced radioresistance associated with the activation of epithelial-mesenchymal transition by stress hormone-stimulated adrenergic receptors.

中文翻译：

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心理压力可促进肺癌临床前模型中的肿瘤生长并减弱放射反应

背景和目的 患有危及生命的疾病（如癌症）的患者会经历情绪困扰。本研究旨在探讨相关心理压力源对肿瘤生长和治疗抵抗的分子和细胞机制。材料和方法 通过暴露于接受不可避免的足部电击的同种小鼠，在携带 LLC 肺肿瘤的 C57BL/6J 小鼠中诱导应激。小鼠连续 3 天接受 7 Gy 的照射。通过旷场测试 (OFT)、高架十字迷宫 (EPM)、蔗糖偏好测试 (SPT) 和习得性无助 (LH) 测试来监测行为。通过蛋白质印迹测量组织和培养细胞中的蛋白质表达。结果 本项动物研究表明，观察一只接受足部电击的同种小鼠会诱发抑郁样行为，血浆皮质酮和肾上腺素水平增加，从而增加肿瘤生长和放射抗性。压力增加了肿瘤组织中 Wnt1、Drosha 和波形蛋白的表达并降低了 E-钙粘蛋白的表达。应力和辐射的结合增强了辐射抗性以及波形蛋白表达的增加。体外研究表明，β2-肾上腺素能受体 (β2-AR) 激动剂可阻断辐射诱导的细胞凋亡并降低细胞活力，同时沉默 β2-AR 表达会降低 β2-AR 激动剂的保护作用。β2-AR 激动剂明显增加了 LLC-1 细胞中 Wnt1 和 Drosha 的表达。