慢性应激促进肿瘤进展和转移的机制及其治疗现状  

Chronic Stress Promotes Tumor Progression and Metastasis:From Mechanisms to Therapeutic Strategies

作　　者：于盼 姚嘉良 田建辉[1] YU Pan;YAO Jialiang;TIAN Jianhui(Clinical Oncology Center,Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Institute of Oncology,Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属市中医医院肿瘤临床医学中心,上海中医药大学附属市中医医院肿瘤研究所,上海200032

出　　处：《肿瘤防治研究》2025年第4期324-330,共7页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金(82305069);上海市卫健委领军人才项目(2022LJ014);上海申康医院发展中心第二轮研究型医师创新转化能力培训项目(SHDC-2023CRD01);2023年度上海中医药大学科技发展项目(23KFL096);上海市中医神志病研究所2023年度开放科研项目(SZB2023102);上海市中医医院未来计划科技发展项目(WL-HBRC-2021001K)。

摘　　要：转移是导致肿瘤患者死亡的关键原因,大量肿瘤患者合并精神心理异常,即处于慢性应激状态。慢性应激通过下丘脑-垂体-肾上腺轴和交感神经系统影响多种激素和神经递质的释放,如肾上腺素、去甲肾上腺素、多巴胺、糖皮质激素、皮质醇、性激素等,这些物质可作用于肿瘤细胞、免疫细胞及肿瘤微环境中其他细胞上的β-肾上腺素能受体、糖皮质激素受体等,通过直接增强肿瘤细胞的侵袭转移能力,诱导免疫抑制微环境的形成,促进肿瘤血管生成等途径促进肿瘤的进展和转移。基于上述机制,抗精神病药物、β-受体阻滞剂、糖皮质激素受体拮抗剂对慢性应激介导的肿瘤转移具有抑制作用,并取得了一定的临床疗效。此外,中药复方和单体也开展了相关的研究,可通过调控免疫微环境和逆转慢性应激介导的激素改变抑制肿瘤转移。肿瘤患者的心理问题逐步受到重视,基于慢性应激促进肿瘤进展和转移的作用机制,开发抗转移新药为肿瘤整体防治效率的提高提供了新的思路。Metastasis is a key cause of death in tumor patients,and a number of tumor patients have comorbid psychosomatic abnormalities and are in a state of chronic stress.Chronic stress affects the release of many kinds of hormones and neurotransmitters,such as epinephrine,norepinephrine,dopamine,glucocorticoids,cortisol,sex hormones,etc.,through the hypothalamus–pituitary–adrenal axis and sympathetic nervous system.These substances can act on theβ-adrenergic receptor,glucocorticoid receptor,etc.,on tumor cells,immune cells,and other cells in the tumor microenvironment and promote the tumor progression and metastasis by directly enhancing the invasive and metastatic ability of tumor cells,inducing the formation of the immunosuppressive microenvironment and promoting tumor angiogenesis and other pathways.Antipsychotic drugs,β-blockers,and glucocorticoid receptor antagonists have inhibitory effects on chronic stressmediated tumor metastasis and have achieved certain clinical efficacy.Relevant studies have been carried out on traditional Chinese medicine decoctions and monomers,which can inhibit tumor metastasis by modulating the immune microenvironment and reversing chronic stress-mediated hormonal changes.The psychological problems of tumor patients have gradually received attention,and the development of new anti-metastatic drugs based on the mechanism of action of chronic stress in promoting tumor progression and metastasis provides new ideas for the improvement of the overall efficiency of tumor prevention and treatment.

关 键 词：肿瘤 转移 慢性应激 免疫 Β-肾上腺素能受体 糖皮质激素受体 治疗现状 

分 类 号：R730.1[医药卫生—肿瘤] R730.58[医药卫生—临床医学]