[關(guān)鍵詞]
[摘要]
和厚樸酚及厚樸酚是疏水性烯丙基聯(lián)苯酚類結(jié)構(gòu)的同分異構(gòu)體,均有抗肺癌藥理作用。和厚樸酚能抑制肺癌A549細胞、H1299細胞和Lewis細胞移植瘤在小鼠體內(nèi)的生長和轉(zhuǎn)移,而厚樸酚能預防烏拉坦誘導小鼠發(fā)生肺癌和抑制A549細胞移植瘤在小鼠體內(nèi)生長。和厚樸酚及厚樸酚在體外能濃度相關(guān)地抑制人小細胞肺癌N446細胞、H446細胞,非小細胞肺癌中的肺腺癌A549、H1299、H441、H1975、Calu3、A2、PC、SPC-A-1、95D細胞,大細胞肺癌H460細胞,人肺鱗癌H226、H520、CH27細胞以及小鼠肺癌Lewis細胞增殖,并誘導其凋亡和壞死。和厚樸酚及厚樸酚抑制肺癌的主要機制是:(1)抑制I型去乙?;傅谋磉_和酶活性,上調(diào)死亡受體-5(DR5)的表達,激活腫瘤壞死因子相關(guān)的凋亡誘導配體(TRAIL)信號通路;(2)激活與半胱天冬酶無關(guān)的凋亡通路;(3)阻滯癌細胞中的微管聚合,破壞微管結(jié)構(gòu);(4)阻滯蛋白激酶B(AKT)/哺乳動物雷帕霉素靶蛋白(mTOR)信號通路,誘導癌細胞自噬;(5)阻滯磷脂酰肌醇-3激酶(PI3K)/AKT信號通路而抑制癌細胞轉(zhuǎn)移。
[Key word]
[Abstract]
Honokiol and magnolol are hydrophobic isomers of propenyl biphenol-type structure. Honokiol can treat for growth and metastasis of lung cancer A549 cells, H1299cells and Lewis cells transplantation tumor in mice. Magnolol can prevent urethane from inducing lung cancer in mice, and can treat for growth of A549 cells transplantation tumor in mice. In vitro honokiol and magnolol inhibit proliferation and induce apoptosis and necrosis in association with dosage on human small cell lung cancer N446 cells, H446 cells, and human lung adenocarcinoma A549 cells, H1299 cells, H441 cells, H1975 cells, Calu3 cells, A2 cells, PC-9 cells, SPC-A-1 cells, 95D cells, and human large cell lung cancer H460 cells, and human lung squamous carcinoma H226 cells, H520 cells, CH27 cells, and mouse lung cancer Lewis cells. The mechanisms of honokiol and magnolol against lung cancer are inhibiting the expression of class I deacetylase and its enzyme activity to up-regulate the expression of DR5 and to activate TRAIL signaling pathway, and activating caspase-independent apoptosis pathway, and inhibiting microtubule polymerization to destroy microtubule structure, and inhibiting AKT/mTOR signaling pathway to induce autophagy of cancer cells, and inhibiting PI3K/AKT signaling pathway to block metastasis of cancer cells.
[中圖分類號]
R285.5
[基金項目]