内质网应激对肿瘤发生发展的影响及中医药的干预作用

Effect of Endoplasmic Reticulum Stress on Tumorigenesis and Development and Intervention of Traditional Chinese Medicine:A Review

内质网是真核细胞内负责蛋白质、类固醇、脂类和糖类合成以及钙依赖性信号转导的重要细胞器,内质网稳态对维持机体正常功能具有重要意义。内质网稳态失衡可诱发内质网应激(ERS),参与消化系统、呼吸系统、循环系统、神经系统、生殖系统和内分泌系统等疾病的发生与发展,影响机体健康。在众多疾病中,肿瘤的致死率、致残率和复发率均较高,严重危及国民健康。因异于正常细胞的无限增殖的生存特点,肿瘤细胞常暴露于缺氧、缺血、增殖过度、饥饿等各种内外刺激中,导致细胞内蛋白质平衡遭到破坏,存在一定程度ERS,以促进自身存活。研究表明,ERS在多种肿瘤中扮演重要角色,对肿瘤细胞的生存具有双重作用,既可通过激活一系列适应性反应促进肿瘤细胞生存,又可诱发ERS相关凋亡通路,促进肿瘤细胞死亡,抑制肿瘤生长和侵袭。而随着ERS在肿瘤中的多种作用不断被报道,较多学者已尝试从ERS的角度干预肿瘤的进展。中医药对肿瘤的治疗作用已得到广泛认可,能从多个方面参与肿瘤的调节,包括ERS,放化疗抵抗,化疗致胃肠道不良反应,术后复发和转移等。但目前,从ERS角度探究中医药抗肿瘤作用报道相对较少。鉴于此,本文从ERS对肿瘤发生发展的影响和中医药经ERS干预肿瘤的进展2个方面进行阐述,以期为肿瘤的治疗提供新的方向。

Endoplasmic reticulum(ER)is an important organelle responsible for protein,steroid,lipid and carbohydrate synthesis and calcium-dependent signal transduction in eukaryotic cells. ER homeostasis is essential for normal cell function. ER homeostasis imbalance can induce ER stress(ERS),which participates in the occurrence and development of diseases of the digestive system,respiratory system,circulatory system,nervous system,reproductive system,and endocrine system,and affects body health. Among various diseases,cancers seriously endanger people ′s health due to its high mortality rate,disability rate,and recurrence rate. Due to the survival characteristics of unlimited proliferation,tumor cells are often exposed to various internal and external stimuli such as hypoxia,ischemia,excessive proliferation,and starvation,which destroy intracellular protein balance and induce ERS to some extent for survival. ERS plays a major role in various tumors and has dual functions in the survival of tumor cells:promoting the survival of tumor cells by activating a series of adaptive responses,while inducing ERS-related apoptosis pathways,so as to promote tumor cell death and inhibit tumor growth and invasion. As multiple functions of ERS in tumors are reported,many scholars have tried to intervene in the progress of tumors from the perspective of ERS. The therapeutic effect of traditional Chinese medicine(TCM)on tumors has been widely recognized. TCM can participate in the regulation of tumors from many aspects,including ERS,chemoradiotherapy resistance,gastrointestinal adverse reactions caused by chemotherapy,postoperative recurrence and metastasis. Since there are few reports on the antitumor effect of TCM from the perspective of ERS,this paper expounds the influence of ERS on tumorigenesis and development and the progress of TCM intervention in tumor through ERS,in order to provide a new direction for tumor treatment.