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缺氧条件下Netrin-1通过激活PI3KAKT通路诱导宫颈癌细胞上皮-间质转化 被引量:2

Netrin-1 induces epithelial-mesenchymal transition of cervical cancer through activating PI3K/AKT signaling pathway under hypoxic conditions
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摘要 目的探讨缺氧条件下Netrin-1通过激活PI3K/AKT通路诱导宫颈癌细胞上皮-间质转化(EMT)。方法qPCR检测正常上皮细胞HaCaT及宫颈癌细胞系SiHa、Caski、Hela中Netrin-1的表达。二氧化钴处理模拟低氧微环境,通过Transwall和细胞划痕实验观察SiHa、Caski、Hela细胞侵袭及迁移能力,蛋白免疫印迹法(Western Blot)检测Netrin-1及EMT标志物E-cadherin、Vimentin蛋白表达变化。采用小干扰RNA(Si-Netrin-1)转染SiHa细胞,检测E-cadherin、Vimentin、AKT、p-AKT蛋白表达及细胞侵袭、迁移能力的变化。结果Netrin-1在宫颈癌细胞系中高表达,且低氧条件下显著增强Netrin-1的表达(P<0.01)。低氧条件下SiHa、Caski细胞中E-cadherin蛋白显著下调,Vimentin蛋白显著上调,细胞的侵袭及迁移能力显著增强,PI3K/AKT通路被激活。在SiHa细胞中敲低Netrin-1,抑制低氧诱导SiHa细胞的上皮-间质转化过程。结论缺氧条件下,Netrin-1可通过激活PI3K/AKT通路诱导宫颈癌细胞上皮-间质转化过程。 Objective To explore the effect of Netrin-1 on the induction of cervical cancer epithelial-mesenchymal transition(EMT)by activating the PI3K/AKT pathway under hypoxic conditions.Methods The expression of Netrin-1 in normal HaCaT epithelial cells and SiHa,Caski and Hela cervical cancer cell lines were detected.The cobalt dioxide treatment simulated the hypoxic microenvironment.The invasive and migratory ability of SiHa,Caski and Hela cells were detected through Transwell assay and cell wound healing assay.The expression of Netrin-1and EMT markers(E-cadherin and Vimentin)was examined using Western Blotting.SiHa cells were transfected with small interfering RNA(Si-Netrin-1)to detect the expression of E-cadherin,Vimentin,AKT,p-AKT proteins and the changes in cell invasive and migratory capabilities.Results Netrin-1 was highly expressed in cervical cancer cell lines,and the expression of Netrin-1 was significantly enhanced under hypoxic conditions(P<0.01).E-cadherin was significantly down-regulated and Vimentin was up-regulated in SiHa and Caski cells under hypoxic conditions,cell invasive and migratory capabilities were also significantly enhanced,in addition,PI3K/AKT signaling pathway was activated.Netrin-1 knockdown inhibited EMT of SiHa cells induced by hypoxia.Conclusion Netrin-1 induces epithelial-mesenchymal transition of cervical cancer through activating PI3K/AKT signaling pathway under hypoxic conditions.
作者 张晓涵 迟淑娜 徐征鹏 ZHANG Xiaohan;CHI Shuna;XU Zhengpeng(Department of Gynecological Tumor, Clinical College of Binzhou Medical College, Yantai 264000, Shandong, China)
出处 《西部医学》 2022年第3期340-346,共7页 Medical Journal of West China
基金 山东省自然科学基金(JQ201718)。
关键词 宫颈癌 低氧 NETRIN-1 上皮-间质转化 PI3K/AKT Cervical cancer Hypoxic Netrin-1 Epithelial-mesenchymal transition PI3K/AKT
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