基于PI3K/AKT信号通路探讨中医药治疗肺癌研究进展

Research Progress in Traditional Chinese Medicine Treatment of Lung Cancer Based on PI3K/AKT Signaling Pathway

磷脂酰肌3-激酶(phosphatidylinositol 3 kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)信号通路是生物体内重要的信号转导系统之一,具有调节细胞生长、分化、凋亡等多种功能,与肺癌细胞的增殖、凋亡、自噬、侵袭转移、上皮-间质转化(epithelial-mesenchymal transformation,EMT)等细胞活动密切相关。中医药可以通过干预PI3K/AKT通路及其相关靶点蛋白调节细胞周期蛋白与凋亡相关蛋白的表达,从而抑制增殖、诱导凋亡;通过上调自噬相关蛋白的表达,促进肺癌细胞自噬;通过下调基质金属蛋白酶(matrix-metalloproteinase,MMP)的表达,降低肺癌细胞侵袭转移能力;通过多靶点、多机制逆转EMT和耐药。但是,中医药基于PI3K/AKT信号通路治疗肺癌的研究也存在许多不足:(1)PI3K/AKT信号通路与多条通路纵横交错,许多研究发现,中医药可以同时影响多条信号通路的表达,但各条通路之间的相互影响与相互作用尚未阐明。(2)PI3K/AKT信号通路作用广泛,多数研究仅证实中医药的抗肺癌作用与通路中关键蛋白的表达水平具有相关性,但进一步的作用机制研究较少。(3)此类研究局限于细胞实验和动物实验,缺乏高质量的临床对照试验来验证。未来需要更多的临床和基础研究进一步探讨中医药抗肺癌的作用机制。

The phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)signaling pathway is one of the important signal transduction systems in organisms,which has various functions such as regulating cell growth,differentiation,and apoptosis,and is related to the proliferation,apoptosis,autophagy,invasion and metastasis,and epithelial-mesenchymal transformation of lung cancer cells transformation,EMT)and other cellular activities are closely related.Traditional Chinese medicine can regulate the expression of cyclins and apoptosis-related proteins by intervening in the PI3K/AKT pathway and its related target proteins,thereby inhibiting proliferation and inducing apoptosis.Promote autophagy in lung cancer cells by upregulating the expression of autophagy-related proteins;By down-regulating the expression of matrix-metalloproteinase(MMP),the invasion and metastasis ability of lung cancer cells was reduced.Reversal of EMT and drug resistance through multiple targets and mechanisms.However,there are also many shortcomings in the research of traditional Chinese medicine in the treatment of lung cancer based on PI3K/AKT signaling pathway:(1)PI3K/AKT signaling pathway is crisscrossed with multiple pathways,and many studies have found that traditional Chinese medicine can affect the expression of multiple signaling pathways at the same time,but the interaction and interaction between these pathways have not been clarified.(2)The PI3K/AKT signaling pathway has a wide range of effects,and most studies have only confirmed that the anti-lung cancer effect of traditional Chinese medicine is correlated with the expression level of key proteins in the pathway,but there are few further studies on the mechanism of action.(3)Such studies are limited to cell experiments and animal experiments,and there is a lack of high-quality clinical controlled trials to validate.In the future,more clinical and basic research is needed to further explore the mechanism of action of TCM against lung cancer.