RAB2A通过AKT/CDC42信号通路调控肿瘤微环境对子宫颈癌细胞侵袭转移的影响OA
RAB2A regulates the effect of tumor microenvironment on invasion and metasta-sis of cervical cancer cells through AKT/CDC42 signaling pathway
目的 探讨RAB2A通过AKT/CDC42信号通路调控肿瘤微环境,对子宫颈癌细胞侵袭转移的影响及可能机制.方法 培养人正常子宫颈上皮细胞H8、子宫颈癌细胞Caski、HeLa、ME-180及C33A细胞,采用RT-qPCR检测细胞中RAB2A、AKT、CDC42的mRNA水平,筛选ME-180细胞继续培养,分为子宫颈癌组、低表达RAB2A(Low RAB2A)组及低表达RAB2A+激活AKT(Low RAB2A+AKT activation)组.利用Western blot检测ME-180细胞中RAB2A、AKT、CDC42、HIF-1α、Notch-1和Hes-1的蛋白水平.运用免疫荧光染色检测ME-180细胞中HIF-1α、Notch-1和Hes-1蛋白水平,应用Transwell实验检测ME-180细胞侵袭能力;划痕实验检测ME-180细胞迁移能力.结果 与H8细胞相比,子宫颈癌细胞Caski、HeLa、ME-180及C33A中RAB2A、AKT、CDC42的mRNA表达增加(P<0.05),其中ME-180细胞的RAB2A、AKT、CDC42的mRNA表达最为显著.与H8细胞相比,子宫颈癌细胞ME-180中HIF-1α、Notch-1和Hes-1蛋白表达增加.与子宫颈癌组相比,Low RAB2A组子宫颈癌细胞ME-180中RAB2A、AKT、CDC42蛋白水平减少(P<0.05),细胞的侵袭及迁移能力降低(P<0.05),HIF-1α、Notch-1和Hes-1蛋白表达减少(P<0.05);与Low RAB2A组相比,Low RAB2A+AKT activation组子宫颈癌细胞中HIF-1α、Notch-1和Hes-1蛋白表达增加(P<0.05).结论 RAB2A可激活AKT/CDC42信号通路调控肿瘤微环境,促进子宫颈癌细胞的侵袭转移.
Objective To investigate the effect and its possible mechanism of RAB2A on the invasion and metas-tasis of cervical cancer cells by regulating tumor microenvironment via AKT/CDC42 signaling pathway.Methods Human normal cervical epithelial cells(H8),cervical cancer cells(Caski,HeLa,ME-180 and C33A)were cul-tured.RT-qPCR was used to assess RAB2A,AKT,and CDC42 mRNA levels,leading to the selection of ME-180 cells for subsequent experiments.These cells were divided into three groups:cervical cancer,RAB2A-knockdown(Low RAB2A),and RAB2A-knockdown with AKT activation(Low RAB2A+AKT activation).Protein expression levels of RAB2A,AKT,CDC42,HIF-1α,Notch-1,and Hes-1 were analyzed by Western blot.Immunofluorescence was used to detect HIF-1α,Notch-1,and Hes-1.Cell invasion and migration abilities were evaluated by Transwell assay and wound scratch test,respectively,scratch test to detect the migration ability of ME-180 cells.Results RAB2A,AKT,and CDC42 mRNA levels were significantly higher in cervical cancer cells(Caski,HeLa,ME-180 and C33A)compared to H8 cells(P<0.05),with the most pronounced increase observed in ME-180 cells.Protein levels of HIF-1α,Notch-1,and Hes-1 were also increased in ME-180 cells compared to H8 cells.Compared with the cervical cancer group,Low RAB2A led to decreased expression of AKT,CDC42,HIF-1α,Notch-1,and Hes-1 pro-teins(P<0.05),and significantly inhibited cell invasion and migration(P<0.05).The expressions of HIF-1α,Notch-1 and Hes-1 proteins in the Low RAB2A+AKT activation group were increased compared to the Low RAB2A group(P<0.05).Conclusion RAB2A can activate AKT/CDC42 signaling pathway to regulate tumor microenviron-ment and promote invasion and metastasis of cervical cancer cells.
陈奕至;夏露花
首都医科大学附属北京世纪坛医院病理科,北京 100038新疆肿瘤学重点实验室/新疆医科大学附属肿瘤医院核医学科,乌鲁木齐 830011
医药卫生
子宫颈肿瘤RAB2AAKT/CDC42通路肿瘤微环境侵袭迁移
cervical neoplasmsRAB2AAKT/CDC42 pathwaytumor microenvironmentinvademigration
《临床与实验病理学杂志》 2026 (2)
177-182,189,7
首都卫生发展科研专项(2024-2-8011) Capital Health Development Research Special Project(2024-2-8011)
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