南京医科大学学报(自然科学版)2025,Vol.45Issue(6):777-785,9.DOI:10.7655/NYDXBNSN241268
Akt1上调FBXO6表达对胶质瘤细胞增殖和侵袭的影响
The effects of Akt1 upregulated FBXO6 expression on the proliferation and invasive of glioma cells
摘要
Abstract
Objective:To examine the expression of F-box protein(FBXO)6 in glioma tissues and cells and its impact on the proliferation and invasion of glioma cells,and to explore the upstream regulatory mechanism of FBXO6 expression.Methods:The CGGA database was used to analyze the expression of FBXO6 in tumor tissues of glioma patients and its correlation with patient prognosis.RT-PCR and Western blot were performed to check the expression levels of FBXO6 in glioma cell lines(U251,U373,and U87),and U87 cells with the highest expression were screened out.RT-PCR,Western blot,CCK-8,and Transwell experiments were carried out to detect the effects of FBXO6 overexpression and silencing on the proliferation and invasion of U87 cells.U87 cells were treated with U0126(an ERK1/2 inhibitor),SP600125(a JNK inhibitor),and Perifosine(an Akt1 inhibitor),and Western blot was conducted to examine the expression and phosphorylation levels of ERK1/2,JNK and Akt1.Subsequently,RT-PCR and Western blot were used to detect the expression changes of FBXO6,and then CCK-8 and Transwell experiments were performed to measure the proliferation and invasion capabilities of U87 cells.FBXO6 was overexpressed in U87 cells,which were then treated with Perifosine,and RT-PCR,Western blot,CCK-8,and Transwell experiments were carried out to investigate the levels of FBXO6 expression,cell proliferation,and invasion.Results:FBXO6 is highly expressed in glioma tissue,and its expression level is positively correlated with the degree of malignancy.It is also closely associated with the poor prognosis of patients.All three glioma cell lines,namely U251,U373,and U87,expressed FBXO6,with U87 cells showing the most significant expression.The proliferation and invasion of U87 cells were significantly enhanced after FBXO6 overexpression,while these were significantly weakened after FBXO6 silencing.The Akt1 inhibitor could significantly down-regulate the expression of FBXO6 in U87 cells,whereas the ERK1/2 and JNK inhibitors had no significant effect on FBXO6 expression.The Akt1 inhibitor could significantly reduce the proliferation and invasion of U87 cells,and FBXO6 overexpression could antagonize the above effects.Conclusion:Activation of Akt1 in glioma cells up-regulates the expression of the FBXO6 gene,promoting cell proliferation and invasion.关键词
胶质瘤/FBXO6/Akt1/增殖/侵袭Key words
glioma/FBXO6/Akt1/proliferation/invasion分类
临床医学引用本文复制引用
高彩月,曹丹丹,倪思琦,张婧,王迎伟,邱文,赵晨卉..Akt1上调FBXO6表达对胶质瘤细胞增殖和侵袭的影响[J].南京医科大学学报(自然科学版),2025,45(6):777-785,9.基金项目
国家自然科学基金(81902878) (81902878)
江苏省高等学校大学生创新训练计划项目(202010312039Y) (202010312039Y)