Saponins from the Roots of Platycodon grandiflorum Suppresses TGFβ1-Induced Epithelial-Mesenchymal Transition Via Repression of PI3K/Akt, ERK1/2 and Smad2/3 Pathway in Human Lung Carcinoma A549 Cells
Saponins from the Roots of Platycodon grandiflorum Suppresses TGFβ1-Induced Epithelial-Mesenchymal Transition Via Repression of PI3K/Akt, ERK1/2 and Smad2/3 Pathway in Human Lung Carcinoma A549 Cells
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DOI：
10.1080/01635581.2014.853087
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发表时间：
2014-01-01
影响因子：
2.9
通讯作者：
Jeong, Hye Gwang
中科院分区：
文献类型：
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作者：
Choi, Jae Ho;Hwang, Yong Pil;Jeong, Hye Gwang
转化生长因子是一种多功能细胞因子，通过激活Smad和非Smad信号通路诱导生长停滞、组织纤维化和上皮-间充质转化(EMT)。EMT是分化开关，极化的上皮细胞通过它分化为收缩和运动的间充质细胞。我们以前的研究表明，桔梗根皂苷(CKS)具有抗炎、抗氧化、抗肿瘤转移和保护肝脏的作用。在本研究中，我们研究了CKS对TGF1诱导的人肺癌A549细胞EMT改变的抑制作用。我们发现，CKS处理的细胞显示出抑制TGF1介导的E-钙粘蛋白下调和Vimentin上调的作用，并保留了上皮的形态。此外，CKS还可降低TGF1上调的Snail表达，Snail是E-钙粘蛋白的抑制因子，也是EMT的诱导者。CKS抑制TGF1诱导的Akt、ERK1/2和糖原合成酶-3(GSK-3)的磷酸化。抑制PI3K/Akt和ERK1/2也可阻断TGF1诱导的GSK-3磷酸化和Snail激活。此外，Akt和ERK1/2的选择性抑制剂可降低TGF1诱导的Snail表达。此外，CKS还可减弱TGF1诱导的Smad2/3磷酸化和上调Smad7的表达。这些结果表明，CKS可抑制TGF1通过PI3K/Akt、ERK1/2、GSK-3和Smad2/3途径诱导的人肺癌细胞EMT。
Transforming growth factor (TGF) is a multifunctional cytokine that induces growth arrest, tissue fibrosis, and epithelial-mesenchymal transition (EMT) through activation of Smad and non-Smad signaling pathways. EMT is the differentiation switch by which polarized epithelial cells differentiate into contractile and motile mesenchymal cells. Our previous studies have shown that saponins from the roots of Platycodon grandiflorum (CKS) have antiinflammatory, antioxidant, antimetastatic, and hepatoprotective effects. In this study, we investigated the inhibitory effect of CKS on TGF1-induced alterations characteristic of EMT in human lung carcinoma A549 cells. We found that CKS-treated cells displayed inhibited TGF1-mediated E-cadherin downregulation and Vimentin upregulation and also retained epithelial morphology. Furthermore, TGF1-increased Snail expression, a repressor of E-cadherin and an inducer of the EMT, was reduced by CKS. CKS inhibited TGF1-induced phosphorylation of Akt, ERK1/2, and glycogen synthase kinase-3 (GSK-3). Inhibition of PI3K/Akt and ERK1/2 also blocked TGF1-induced GSK-3 phosphorylation and Snail activation. Furthermore, TGF1-increased Snail expression was reduced by selective inhibitors of Akt and ERK1/2. Moreover, CKS treatment attenuated TGF1-induced Smad2/3 phosphorylation and upregulated Smad7 expression. These results indicate that pretreatment with the CKS inhibits the TGF1-induced EMT through PI3K/Akt, ERK1/2, GSK-3 and Smad2/3 in human lung carcinoma cells.