Departamento de Bienestar y Desarrollo Sustentable, Centro Universitario del NORTE, Carretera Federal No. 23, Km 191, C.P. 46200, Colotlán, Jalisco, México.
Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Carretera Guadalajara-Nogales Km 15.5, Las Agujas, C.P. 45110, Zapopan, Jalisco, México.
Mol Biol Rep. 2020 Dec;47(12):9429-9439. doi: 10.1007/s11033-020-06022-0. Epub 2020 Dec 1.
Biological response to stress depends on the type, timing, and severity of the stressor. Acute stressful environments may positively activate molecular and cellular mechanisms to favor adaptation; however, chronic stress is often associated with detrimental health effects. Colon cancer (CC) is one of the leading causes of death associated with cancer and has been mentioned as a stress-related disease. In the present work, the effect of chronic stress on the initial phase of CC was evaluated, and special emphasis was placed on ornithine decarboxylase (ODC) expression and polyamines for their role in hyperproliferative diseases. BALB/c mice (n = 5/group) were administered the pro-carcinogen 1,2-dimethylhydrazine (DMH) for 8 weeks (20 mg/kg body weight/week) to induce colon carcinogenesis, and then exposed for 4 weeks to two physical stressors: restraint and forced-swimming. Distal colon inflammatory lesions and histomorphological changes were evaluated by hematoxylin-eosin staining; plasma corticosterone levels, colon ODC expression, and urinary polyamines were determined by competitive ELISA, RT-qPCR, Western Blot, and HPLC, respectively. The short-term exposure to DMH triggered colon inflammation, initiated colon carcinogenesis and increased ODC expression; meanwhile, the exposure to chronic stress activated the hypothalamic-pituitary-adrenal (HPA) axis, elicited the production of plasmatic corticosterone, and decreased ODC expression. The exposure of DMH-treated mice to chronic stress counteracted the inflammatory effect of DMH and maintained ODC homeostasis. In early phase of carcinogenesis, the exposure of DMH-treated mice to chronic stress had a positive effect against colon inflammation and maintained ODC homeostasis. The cross-talk between corticosterone, ODC expression, and inflammation in a tumor environment is discussed.
生物对压力的反应取决于压力源的类型、时间和严重程度。急性应激环境可能会积极激活分子和细胞机制，有利于适应；然而，慢性应激通常与有害的健康影响有关。结肠癌（CC）是癌症相关死亡的主要原因之一，并且被认为是一种与压力相关的疾病。在本工作中，评估了慢性应激对 CC 初始阶段的影响，并特别强调了鸟氨酸脱羧酶（ODC）的表达和多胺在促增殖性疾病中的作用。BALB/c 小鼠（n = 5/组）给予促癌剂 1,2-二甲基肼（DMH）8 周（20 mg/kg 体重/周）以诱导结肠癌发生，然后暴露于两种物理应激源 4 周：束缚和强迫游泳。通过苏木精-伊红染色评估远端结肠炎症病变和组织形态学变化；通过竞争性 ELISA、RT-qPCR、Western Blot 和 HPLC 分别测定血浆皮质酮水平、结肠 ODC 表达和尿多胺。DMH 的短期暴露引发结肠炎症，启动结肠癌变并增加 ODC 表达；同时，慢性应激暴露激活下丘脑-垂体-肾上腺（HPA）轴，引起血浆皮质酮的产生，并降低 ODC 表达。DMH 处理小鼠暴露于慢性应激可抵消 DMH 的炎症作用并维持 ODC 平衡。在癌变的早期阶段，DMH 处理小鼠暴露于慢性应激对结肠炎症具有积极作用并维持 ODC 平衡。讨论了皮质酮、ODC 表达和肿瘤环境中炎症之间的串扰。
