Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, PR China; Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, USA.
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, USA.
Radiother Oncol. 2020 May;146:126-135. doi: 10.1016/j.radonc.2020.02.004. Epub 2020 Mar 6.
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.
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.
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 β-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.
Psychological stress increased tumor growth and enhanced radioresistance associated with the activation of epithelial-mesenchymal transition by stress hormone-stimulated adrenergic receptors.
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应激源对肿瘤生长和治疗抵抗的分子和细胞机制。
通过暴露于接受无法逃避的足部电击的同种小鼠，在携带 LLC 肺肿瘤的 C57BL/6J 小鼠中诱发应激。小鼠连续 3 天接受 7Gy 的照射。通过旷场试验（OFT）、高架十字迷宫（EPM）、蔗糖偏好试验（SPT）和习得性无助（LH）试验监测行为。通过 Western blot 测量组织和培养细胞中的蛋白质表达。
本动物研究表明，观察到同种小鼠接受足部电击会引起抑郁样行为，导致血浆皮质酮和肾上腺素水平升高，从而促进肿瘤生长和放射抵抗。应激增加了肿瘤组织中的 Wnt1、Drosha 和波形蛋白表达，降低了 E-钙黏蛋白表达。应激和照射的联合增强了放射抵抗，同时增加了波形蛋白表达。体外研究表明，β-肾上腺素能受体（β2-AR）激动剂阻断了照射诱导的细胞凋亡并降低了细胞活力，而沉默β2-AR 表达则降低了β2-AR 激动剂的保护作用。β2-AR 激动剂明显增加了 LLC-1 细胞中的 Wnt1 和 Drosha 表达。
心理应激通过应激激素刺激的肾上腺素能受体增加上皮-间充质转化，从而增加肿瘤生长并增强放射抵抗。
