中药诱导细胞周期阻滞抗肿瘤研究进展

Anti-tumor Effect of Chinese Medicine by Inducing Cell Cycle Arrest:A Review

癌症患病率和死亡率逐年上升,已成为当今世界上造成死亡的主要原因之一。癌症的诱因多种多样,遗传、辐射、致癌物等都可能诱发癌症,细胞周期调控的异常也是诱因之一。细胞周期是一个复杂的事件序列,细胞通过该事件重复其内容并分裂。细胞周期有高度的组织性和条理性,以确保遗传物质的完整性。该过程依赖于许多基因和蛋白的共同调节,当这些物质发生改变时,细胞周期出现异常,导致细胞增殖失去管控,细胞凋亡被抑制,最终导致肿瘤的发生。目前,肿瘤的治疗手段有传统的手术切除、放射治疗和化学药物治疗及靶向治疗等。中药来源广泛、不良反应小,是中医药文化的瑰宝,值得进一步地研究和开发。越来越多的研究发现,多种中药能够通过诱导细胞周期阻滞发挥抗肿瘤作用,从而提升肿瘤中晚期患者的生存质量,延长患者生存期。该文首先介绍了细胞周期各时期的特点和相关调控因子,列举了细胞周期异常导致肿瘤发生的临床和实验实例,接着综述了国内外靶向细胞周期抗肿瘤热点药物,如周期蛋白依赖性激酶(CDK)抑制剂、细胞分裂周期因子25(CDC25)抑制剂、ATR丝氨酸/苏氨酸激酶(ATR)抑制剂和细胞周期检查点激酶1(CHK1)抑制剂等,最后从细胞周期G0/G1期、S期和G2/M期3个方面切入,总结了近些年来中药通过诱导细胞周期阻滞发挥抗肿瘤作用的相关研究,以期为中药抗肿瘤作用研究提供一定的参考。

The prevalence and mortality of cancer have been on the rise,and it has been the global leading cause of death.The causes of cancer are diverse,such as heredity,radiation,and carcinogens.The abnormality of cell cycle regulation is also one of the causes.Cell cycle is a complex sequence of events through which a cell duplicates its contents and divides.Cell cycle is highly organized to ensure the integrity of genetic material.This process involves many regulatory genes and proteins.Cell cycle will be dysregulated when these proteins and genes change,resulting in the loss of control of cell proliferation,the inhibition of apoptosis,and finally the occurrence of tumor.At the moment,the therapies for cancer include traditional surgical resection,radiotherapy,chemical therapy,and targeted therapy.Chinese medicine has a wide range of sources and little side effect,which is worthy of further research and development.More and more studies have revealed that a variety of Chinese medicines play an anti-tumor role by inducing cell cycle arrest,so as to improve the quality of life and prolong the survival time of patients with advanced tumors.This article first introduces the characteristics and related regulatory factors of each phase of cell cycle,and enumerates the clinical and experimental examples of tumorigenesis caused by abnormal cell cycle.Then,we summarize the hot anti-tumor drugs targeting cell cycle in China and abroad,such as Cyclin-dependent kinase(CDK)inhibitors,cell division cycle 25(CDC25)inhibitors,ataxia-telangiectasia-mutated-and-Rad3-related kinase(ATR)inhibitors,and checkpoint kinase 1(CHK1)inhibitors.Finally,this article summarizes the recent research on the anti-tumor effect of Chinese medicine by inducing cell cycle arrest from the three aspects of cell cycle G0/G1phase,S phase and G2/M phase,in order to provide some reference for the research on the anti-tumor effect of Chinese medicine.