Department of Research Office, Jiangsu Health Vocational College, Nanjing, Jiangsu 211800, P.R. China.
Jiangsu KeyGen Biotech Co., Ltd., Nanjing, Jiangsu 211100, P.R. China.
Oncol Rep. 2019 May;41(5):2975-2986. doi: 10.3892/or.2019.7062. Epub 2019 Mar 13.
Astragaloside IV is the main ingredient of the medicinal herb Radix astragali, which has reported to have antitumor activity in vitro and in vivo. To determine whether the inhibitory effect of astragaloside IV on the invasion and metastasis of the cervical cancer cells is associated with epithelial‑mesenchymal transition (EMT), wound healing and Transwell assays were performed using SiHa cervical cancer cells and demonstrated that astragaloside IV inhibited invasion and migration of human SiHa cervical cancer cells in vitro. Immunocytochemical and western blot analyses indicated that astragaloside IV inhibited EMT by affecting the expression of transforming growth factor‑β1 (TGF‑β1) and E‑cadherin in the cancer cells. Two Smad‑independent pathways mediated by TGF‑β1 were identified to be associated with the effects of astragaloside IV, namely, mitogen‑activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) signaling pathways. The data indicated that astragaloside IV has inhibitory effects on phosphorylation of P38 MAPK, PI3K, AKT and mTOR of SiHa cells of cervical cancer. Furthermore, MAPK and PI3K pathway inhibitors were administered to the cancer cells and the expression of E‑cadherin, a marker of EMT, was determined by reverse transcription‑quantitative polymerase chain reaction. The results demonstrated that MAPK and PI3K pathways were involved in the inhibitory effect of astragaloside IV on EMT. In vivo small animal imaging techniques was performed and demonstrated that astragaloside IV inhibited the metastasis of cervical cancer cells. Taken together, the findings demonstrated that astragaloside IV inhibits the invasion and migration of cervical cancer cells in vitro and in vivo.
黄芪甲苷是中药黄芪的主要成分,已报道其在体外和体内具有抗肿瘤活性。为了确定黄芪甲苷对宫颈癌细胞侵袭和转移的抑制作用是否与上皮-间充质转化(EMT)有关,我们使用 SiHa 宫颈癌细胞进行了划痕愈合和 Transwell 测定,结果表明黄芪甲苷抑制了人 SiHa 宫颈癌细胞的体外侵袭和迁移。免疫细胞化学和 Western blot 分析表明,黄芪甲苷通过影响 TGF-β1(转化生长因子-β1)和 E-钙黏蛋白在癌细胞中的表达来抑制 EMT。鉴定出两条 TGF-β1 介导的 Smad 非依赖性途径与黄芪甲苷的作用有关,即丝裂原活化蛋白激酶(MAPK)和磷脂酰肌醇 3 激酶(PI3K)信号通路。数据表明,黄芪甲苷对 SiHa 细胞中 P38 MAPK、PI3K、AKT 和 mTOR 的磷酸化具有抑制作用。此外,还向癌细胞中添加了 MAPK 和 PI3K 通路抑制剂,并通过逆转录-定量聚合酶链反应测定 EMT 标志物 E-钙黏蛋白的表达。结果表明,MAPK 和 PI3K 通路参与了黄芪甲苷对 EMT 的抑制作用。进行了体内小动物成像技术,并证明黄芪甲苷抑制了宫颈癌细胞的转移。综上所述,这些发现表明黄芪甲苷抑制了宫颈癌细胞的体外和体内侵袭和迁移。