中医药调控胃癌上皮间质转化相关信号通路的研究进展

Research progress in regulating EMT related signal pathway of gastric cancer with TCM medicine

上皮间质转化指上皮到间质细胞的转化。它赋予细胞转移和入侵的能力,包括减少凋亡与衰老,促进免疫抑制,不仅在发育过程中起着关键的作用,而且还参与组织愈合、器官纤维化和癌症发生等过程。它同样也是胃癌发生侵袭转移的重要环节,是导致胃癌患者死亡的关键因素之一。上皮间质转化的发生与相关信号通路的激活关系密切。越来越多的证据表明中医药对癌症转移相关信号通路具有明显的抑制作用,中医药调控转化生长因子-β(Transforming Growth Factor-β,TGF-β)/Smad通路,多通过抑制TGF-β、TGF-β受体(TGF-βR)及下游蛋白的表达来进行。目前的研究显示中医药调控胃癌上皮间质转化的机制局限于磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-丝氨酸/苏氨酸激酶(Akt Serine/Threonine Kinase,Akt)、TGF-β/Smad等经典通路,新的干预信号、具体的分子机制尚不明确,无法推进中医药在临床中的广泛应用。文章对近年来中医药调控胃癌上皮间质转化相关信号通路(包括EMT与TGF-β/Smad通路,Wnt/β-catenin通路,上皮间质转化与PI3K/Akt通路,长链非编码RNA相关信号通路等相关通路)的研究进行综述,并分析中医药调控胃癌上皮间质转化相关信号通路的用药规律,为下一步揭示中医药抗肿瘤的机制提供新思路。

Epithelial mesenchymal transition(EMT)refers to the transformation from epithelium to interstitial cells.It endows cells with the ability to metastasize and invade,including reducing apoptosis and aging,and promoting immunosuppression.It not only plays a key role in the development process,but also participates in tissue healing,organ fibrosis,cancer and other processes.It is also an important link in the invasion and metastasis of gastric cancer,and one of the key factors leading to the death of gastric cancer patients.The occurrence of EMT is closely related to the activation of related signal pathways.More and more evidence shows that TCM medicine has an obvious inhibitory effect on cancer metastasis related signal pathways,and TCM medicine regulates TGF-β/Smad pathway,mostly through inhibition of TGF-β,TGF-βR and downstream proteins.Current research shows that the mechanism of TCM medicine regulating EMT in gastric cancer is limited to classical pathways such as PI3K/Akt,TGF-β/Smad,and the new intervention signals and specific molecular mechanisms are not clear,which cannot promote the wide application of TCM medicine in clinical practice.This paper reviews the research on the regulation of EMT related signal pathway of gastric cancer by TCM medicine(including EMT and TGF-β/Smad pathway,Wnt/β-catenin pathway,EMT and PI3K/Akt pathway,long chain non-coding RNA-related signaling pathway and other related pathways)in recent years,and analyzed the medication rules of TCM medicine regulating EMT-related signaling pathways in gastric cancer,so as to provide new ideas for revealing the anti-tumor mechanism of TCM medicine in the next step.