中药调控蛋白质磷酸化水平对肿瘤发生发展的影响

Effect of Chinese Medicine Regulating Protein Phosphorylation on Tumorigenesis and Development

蛋白质磷酸化修饰是激活蛋白质生物活性参与细胞生命活动的主要途径之一,研究发现,人体内大约30%的蛋白质会经过不同程度、不同位点的磷酸化修饰。若蛋白质磷酸化修饰水平或位点出现异常,则会引起恶性肿瘤的发生与发展。恶性肿瘤一直是危害人类生命健康的疾病,据统计,全球每年有多达1800多万的恶性肿瘤发生以及960多万的死亡病例。随着对蛋白质磷酸化修饰异常在肿瘤发生发展过程中的不断认知,针对蛋白质磷酸化修饰异常的药物研发已经成为肿瘤治疗领域的研究热点。每味中药均可看作一个天然的分子库,其通过多成分、多靶点的优势,参与调控蛋白质磷酸化修饰水平,且副作用小,耐药性低,是目前调控蛋白质磷酸化修饰水平药物研发的主要来源之一。通过对国内外多个数据库的检索发现,从中药中提取的某些单体、部位及单味中药和中药复方均能通过调控蛋白质磷酸化水平影响肿瘤进展,发挥抗肿瘤效果,且效果较好。基于当前国内外中药对蛋白质磷酸化调节的研究现状,笔者整理相关资料发现,中药能通过调节蛋白质磷酸化水平抑制肿瘤细胞增殖、侵袭转移、血管新生及干细胞干性的维持,且通过促进凋亡等方式发挥抗肿瘤效果。为了明晰中药调节蛋白质磷酸化水平发挥抗肿瘤作用的分子机制,为中药抗肿瘤药物的研发及临床应用提供参考,此文对中药调节蛋白质磷酸化水平从不同途径发挥抗肿瘤作用的机制进行了综述。

Protein phosphorylation is one of the main ways to activate protein bioactivity and make it participate in cell life activities. Researches have shown that approximately 30% of proteins in the human body are modified by phosphorylation at different levels and at different sites. If the protein phosphorylation modification level or site is abnormal,it will cause the occurrence and development of malignant tumors.Malignant tumors have always been a kind of diseases that endanger human life and health. According to statistics,as many as 18 million malignant tumors and more than 9.6 million deaths occur every year worldwide.With the continuous recognition on the abnormality of protein phosphorylation modification in tumorigenesis and development,the research and development of drugs for abnormality of protein phosphorylation modification has become a focus in the field of tumor therapy at present. Each traditional Chinese medicine(TCM)can be regarded as a natural molecular library, and it participates in the regulation of protein phosphorylation modification level with the advantages of multiple components and multiple targets,with slight side effect and low drug resistance, so TCM is one of the main sources of drug development for regulating protein phosphorylation modification levels. Through the search of multiple databases at home and abroad,it was found that certain monomers,parts extracted from TCM,single-TCM and TCM compounds can affect the tumor progression by regulating the level of protein phosphorylation and exert better anti-tumor effect. Based on the current research status of protein phosphorylation regulation by TCM at home and abroad,we found that TCM can inhibit tumor cell proliferation, invasion and metastasis, angiogenesis, and maintenance of stem cell stemness by regulating protein phosphorylation levels,and exert antitumor effects by promoting apoptosis. In order to clarify the molecular mechanism of TCM in regulating protein phosphorylation level and exerting antitumor effect,and provide evidences for the development and clinical application of antitumor TCM,the authors reviewed the mechanism of TCM in regulating protein phosphorylation level and exerting their antitumor effect from different ways in this paper.