PI3K/Akt/mTOR信号通路抗非小细胞肺癌的机制及中药干预研究进展

Mechanism of PI3K/Akt/mTOR Signaling Pathway Against Non-small Cell Lung Cancer and Chinese Medicine Intervention:A Review

非小细胞肺癌(NSCLC)是一种发病率较高的呼吸系统恶性肿瘤,早期症状不典型,多数患者确诊时已为晚期,严重威胁人民群众的生命健康。手术、化疗及靶向治疗是目前治疗的主要手段,但随之而来的耐药及不良反应,使得此治疗方式具有了一定的局限性。近年来,随着中医药抗肿瘤的发展和进步,中医药以其治疗效果明显,不良反应少等优势受到了广泛的关注。众多信号通路参与NSCLC的形成与发展,其中磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路是关键的调控通路之一,PI3K/Akt/mTOR信号通路通过影响肿瘤细胞的周期、抑制肿瘤细胞的凋亡、抑制肿瘤细胞的自噬及促进肿瘤新生血管的生成,影响NSCLC细胞的增殖、侵袭和转移。通过检索近年的文献发现,中药可以通过调控PI3K/Akt/mTOR信号通路对NSCLC细胞的自噬、细胞周期、凋亡、侵袭和转移、新生血管的生成及逆转耐药等过程发挥着不可或缺的作用。尽管部分中药提取物或复方在NSCLC治疗方面的一些作用机制已取得较大突破,但这些研究也仅停留在体外细胞实验及动物体内研究层面,研究者们面临着“将中药研究成果转化于临床应用中”这一巨大挑战。基于国内外的研究现状,笔者归纳总结了近年来中药通过调控PI3K/Akt/mTOR信号通路干预NSCLC的研究进展,以期为NSCLC药物治疗研究开拓新的思路,同时也为后续更深入的机制研究提供有益参考。

Non-small cell lung cancer(NSCLC)is a malignant tumor of the respiratory system with a high incidence.The early symptoms are not typical,and most patients are diagnosed at an advanced stage,which seriously threatens the lives and health of people.Surgery,chemotherapy,and targeted therapy are the main means of treatment at present,but the consequent drug resistance and adverse reactions restrict these treatment methods with certain limitations.In recent years,with the development of traditional Chinese medicine(TCM)in tumor resistance,TCM has attracted extensive attention for its obvious therapeutic effect and fewer adverse reactions.Numerous signaling pathways are involved in the formation and development of NSCLC,where phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway is one of the key regulatory pathways.The PI3K/Akt/mTOR signaling pathway affects the proliferation,invasion,and metastasis of NSCLC cells by affecting the cycle,inhibiting the apoptosis,inhibiting the autophagy of tumor cells,and promoting tumor neovascularization.As revealed by the recent literature,Chinese medicine plays an indispensable role in NSCLC cell autophagy,cell cycle,apoptosis,invasion and metastasis,neovascularization,and reversal of drug resistance by regulating the PI3K/Akt/mTOR signaling pathway.Although some Chinese medicinal extracts or compounds have made great breakthroughs in some mechanisms of action in the treatment of NSCLC,these studies only remain at the level of in vitro cell experiments and animal studies in vivo.Researchers are faced with the great challenge of"transforming the research results of Chinese medicines into clinical applications".Based on the current research status in China and abroad,this paper reviewed Chinese medicine in the intervention in NSCLC through the regulation of PI3K/Akt/mTOR signaling pathway in recent years,in order to open up new ideas for NSCLC drug therapy research and also provide a useful reference for further mechanism research.