Saikosaponin D inhibits epithelial mesenchymal transition of
A549 cells via mTOR signaling pathway
SHI Xiao-dong1, ZHENG Jin-xu1, QIAN Hai2, YANG Lei1, SUN Jin-ling1
(1. Department of Respiratory Medicine, the Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001;2.School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013, China )
(1. Department of Respiratory Medicine, the Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001;2.School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013, China )
Abstract:Objective: To study the effect and mechanism of saikosaponin D (SSd) on transforming growth factorβ1(TGFβ1) induced epithelial mesenchymal transition (EMT) in A549 cells. Methods: A549 cells were cultured in vitro, and EMT was induced by TGFβ1 (10 ng/mL). The inhibitory effects of different concentrations of SSd( 0.5, 1.0, 2.0 μmol/L) were observed. Cell proliferation activity was analyzed by MTT assay, protein expression levels of mTOR, p70S6, αsmooth muscle actin (αSMA), Ncadherin, type Ⅰ collagen(collagen Ⅰ) and Ecadherin were detected by Western blotting. Results: The proliferation of A549 cells stimulated by TGFβ1 was enhanced, and SSd significantly reversed the proliferation of TGFβ1stimulated cells in a dosedependent manner. After treatment with SSd, the expression of mTOR and downstream p70S6 protein were significantly decreased in TGFβ1 stimulated A549 cells, and the expression levels of αSMA, collagen Ⅰ and Ncadherin were significantly decreased, while Ecadherin was significantly increased in the dose and timedependent manner. Conclusion: SSd can inhibit A549 cells EMT via a mTOR signaling pathway.
[1]Woodecock HV, Molyneaux PL, maher TM. Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib\[J\]. Drug Des Devel Ther, 2013, 7:503-510.[2]Heldin CH, Moustakas A. Role of Smads in TGFβ signaling\[J\]. Cell Tissue Res, 2012,347(1):21-36.[3]Jechlinger M, Beug H. Mechanisms contribute to epithelial plasticity and metastasis \[J\]. Nat Rew Mol Cell Biol,2003, 4(8):657-665.[4]桂耀松. mTOR信号通路参与肺纤维化发病的机制研究\[D\].北京:北京协和医学院,2013.[5]Nistala R, Sowers JR, WhaleyConnell A. Overnutrition contributes to tubulointerstitial fibrosis by targeting nutrientsensing kinases: role for the mTOR/S6K pathway\[J\]. Cell Cycle, 2012, 11(5):831-832.[6]Zu N,Li P,Li N,et al. Mechanism of saikosaponind in the regulation of rat mesangial cell proliferation and synthesis of extracellular matrix proteins\[J\]. Biochem Cell Biol,2007,85(2):169-174.[7]Hsu YL,Kuo PL,Lin CC. The proliferative inhibition and apoptotic mechanism of Saikosaponin D in human nonsmall cell lung cancer A549 cells\[J\]. Life Sci,2004,75(10):1231-1242.[8]郑金旭,卢坤琴,夏德刚,等. 柴胡皂甙d对博来霉素诱导肺纤维化小鼠的治疗作用及机制研究\[J\]. 中华医学杂志,2010,90(12): 808-812.[9]李远清,彭晖,吴超,等. 高糖通过转化生长因子β信号诱导肾小球内皮细胞向肌成纤维细胞转分化\[J\]. 中华肾脏病杂志,2012,28(12):950-955.[10]Song P, Zheng JX, Liu JZ, et al. Effect of the Wnt1/βcatenin signalling pathway on human embryonic pulmonary fibroblasts\[J\]. Mol Med Rep, 2014, 10(2):1030-1036.[11]Porta C,Paglino C, Mosca A. Targeting PI3K/AKT/mTOR signaling in cancer\[J\]. Front Oncol,2014,4:64.[12]Bachelder RE,Yoon SO, Franci C, et al. Glycogen synthase kinase3 is an endogenous inhabitor of Snail transcription: implication for the epithelial to mensenchymal transition\[J\].J Cell Biol, 2005, 168(1):29-33.[13]李笑,李洪刚,尹崇高. TGFβ1通过PI3K/AKT/mTOR/Snail信号通路促进非小细胞癌SPCA1细胞的上皮间质转化\[J\].中国生物化学与分子生物学报,2015,31(9):710-715.[14]中华医学会呼吸病分会间质性肺疾病学组. 特发性肺纤维化诊断和治疗中国专家共识\[J\]. 中华结核和呼吸杂志,2016,39(6):427-432.