中医药调控细胞衰老发挥抗癌作用的研究进展

Anti-cancer Effect of Traditional Chinese Medicine in Regulating Cellular Senescence:A Review

近年来,癌症的发生率和死亡率不断增加,严重威胁着人类健康。西医主要运用手术切除、化疗、免疫治疗、靶向治疗等治疗手段,但易引发并发症、耐药性及不良反应。越来越多的研究表明,中医药治疗癌症方面有明显优势,可降低癌症的复发率,提高患者的生存质量。细胞衰老是指细胞经过有限次的分裂后不再增殖,进入不可逆的细胞周期停滞状态,导致细胞增殖、分化能力和生理功能衰退,同时伴随细胞形态学改变,如扁平化、多核形态等。在分子水平表现为DNA损伤相关基因表达增多、细胞周期相关因子表达减少及显著的分泌活性等。癌症的恶性发展与细胞衰老密切相关,随着癌细胞增殖次数的不断增加,癌症相关基因发生持续突变,摆脱细胞衰老的束缚,从而实现无限增殖。通过近年来的文献研究发现,诱导肿瘤细胞衰老,可能通过调控细胞的DNA损伤、细胞周期阻滞及衰老相关分泌表型(SASP)等,使抑制性免疫肿瘤微环境向免疫肿瘤微环境激活转化,从而逆转肿瘤细胞衰老的逃逸,是一种颇具前景的癌症治疗策略。然而,细胞衰老在癌症进展中的机制还不完全明确,尤其是中医药调控细胞衰老发挥的抗癌作用。该文从调控细胞衰老的角度,对细胞衰老的具体分子机制、细胞衰老在癌症进展中的作用、基于细胞衰老的中医药抗癌作用机制进行归纳和总结,以期为中医药抗癌作用及新药的研发提供思路与方法。

In recent years,the incidence and mortality rates of cancer have been increasing,posing a serious threat to human health.Western medicine mainly uses treatments such as surgical resection,chemotherapy,immunotherapy and targeted therapy,but they are prone to complications,drug resistance and adverse reactions.A growing number of studies have shown that traditional Chinese medicine has obvious advantages in the treatment of cancer,reducing the recurrence rate of cancer and improving the quality of survival of patients.Cellular senescence refers to a state of irreversible cell cycle growth arrest when cells cease to proliferate after a limited number of divisions,resulting in a decline in cell proliferation and differentiation capacities and physiological functions,accompanied by morphological changes such as flattening and multinuclear morphology.At the molecular level,it shows increased expression of DNA damage-related genes,reduced expression of cell cycle-related factors and significant secretory activity.The malignant development of cancer is closely related to cellular senescence.With the increasing number of cancer cell proliferation,cancerrelated genes undergo continuous mutations,freeing them from cellular senescence and thus achieving unlimited proliferation.Through recent studies,it has been found that induction of tumor cell senescence,possibly through modulation of cellular DNA damage,cell cycle arrest and senescence-associated secretory phenotype(SASP),which converts the suppressive immune tumor microenvironment to an activated immune tumor microenvironment and thus reverses the escape of tumor cell senescence,is a promising strategy for cancer therapy.However,the mechanism of cellular senescence in cancer progression is not fully understood,especially the anti-cancer role played by traditional Chinese medicine in regulating cellular senescence.This article summarized and concluded the specific molecular mechanisms of cellular senescence,the role of cellular senescence in cancer progression,and the mechanism of anti-cancer effects of traditional Chinese medicine based on cellular senescence from the perspective of regulating cellular senescence,with a view to providing ideas and methods for the anti-cancer effects of traditional Chinese medicine and the development of new drugs.