摘要
目的经肿瘤坏死因子样弱凋亡诱导因子(tumor necrosis factor-like weak inducer of apoptosis,TWEAK)作用后,探究巨噬细胞源性外泌体对上皮性卵巢癌细胞侵袭与迁移过程的抑制作用机制。方法对TWEAK在刺激作用前后的巨噬细胞源性外泌体进行收集并得以探究,同高转移人卵巢癌细胞H08910-PM一起进行培养,通过使用实时定量荧光聚合酶链式反应(real-time PCR)对巨噬细胞源性外泌体、巨噬细胞以及共同培养后的HO8910-PM细胞中miRNA-7的表达进行检测,通过Western blotting技术对共培养后的HO8910-PM细胞中表皮生长因子受体(epidermal growth factor recepto,EGFR)/苏氨酸激酶(threonine kinase,AKT)/细胞外调节蛋白激酶(extracellular regulated protein kinase,ERK1)/2信号通路的表达进行检测,经AntagomiR-7,对巨噬细胞内的miRNA-7表达降低进行处理,对经TWEAK作用前后的外泌体进行采集,观察HO8910-PM细胞侵袭和迁移过程中能力的变化情况。结果在TWEAK作用后,观察组巨噬细胞内及其外泌体中miRNA-7表达水平明显高于对照组,巨噬细胞源性外泌体对HO8910-PM细胞中miRNA-7的表达明显高于对照组,差异均有统计学意义(P<0.05)。结论经TWEAK作用巨噬细胞分泌的分泌体后,miRNA-7发挥着重要的影响,可以借助其对上皮性卵巢癌细胞中EGFR信号通路进行抑制从而不断抑制侵袭的全部过程。
Objective To explore the mechanism of macrophage derived exosomes(MDE)inhibiting the invasion and migration of epithelial ovarian cancer(EOC)cells after treatment with tumor necrosis factor-like weak inducer of apoptosis(TWEAK).Methods MDE were collected and explored before and after TWEAK stimulation,and co-cultured with highly metastatic human ovarian cancer cell H08910-PM.The expression of miRNA-7 in MDE,macrophages and co-cultured HO8910-PM cells were detected by real-time PCR.Western blotting was used to detect the expression of epidermal growth factor receptor(EGFR)/threonine kinase(Akt)/extracellular regulated protein kinase(ERK1)/2 signaling pathway in co-cultured HO8910-PM cells.After AntagomiR-7 treatment,the reduced expression of miRNA-7 in macrophages was managed.Exosomes were collected before and after TWEAK treatment to observe the changes of invasion and migration abilities of HO8910-PM cells.Results After TWEAK stimulation,the expression of miRNA-7 in macrophages and their exosomes was increased,and the expression of miRNA-7 in HO8910-PM cells treated by MDE was higher than that in the control group,suggesting significant differences(P<0.05).Conclusion After TWEAK acts on the secretion of macrophages in vivo,miRNA-7 plays an important role in inhibiting EGFR signaling pathway in EOC cells,thereby continuously inhibiting the entire process of invasion.
作者
李霞
张珂
闵楠
LI Xia;ZHANG Ke;MIN Nan(Department of Gynecology, Cancer Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, China)
出处
《河北医科大学学报》
CAS
2021年第2期163-166,共4页
Journal of Hebei Medical University
基金
新疆维吾尔自治区自然科学基金面上项目(2018D01C273)。
关键词
卵巢肿瘤
肿瘤侵润
巨噬细胞
ovarian neoplasms
neoplasm invasiveness
macrophages
