抑制EIF4E下调VEGFA和CCND1的表达以抑制卵巢癌肿瘤进展

Inhibition of EIF4E Down-regulates the Expression of VEGFA and CCND1 to Inhibit the Progression of Ovarian Cancer

目的探讨真核起始因子(Eukaryotic Initiation Factor,EIF)4E在卵巢癌中的作用以及对血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)A和细胞周期蛋白D1(Cyclin D1,CCND1)表达的影响。方法使用SKOV3卵巢癌细胞,分析在线数据以比较卵巢癌患者和正常样本中EIF4E、VEGFA和CCND1的表达差异。进行EIF4E抑制剂4EGI-1的三维细胞培养实验,并通过逆转录定量聚合酶链式(Reverse Transcription-Polymerase Chain Reaction,RT-PCR)技术和Western Blot比较mRNA和蛋白水平。结果癌症基因组图谱(Cancer Genome Atlas,TCGA)显示,卵巢癌患者中VEGFA和CCND1的表达水平显著升高,差异有统计学意义(P均<0.05)。EIF4E与VEGFA和CCND1呈正相关(P均<0.05)。在4EGI-1处理的SKOV3细胞中,EIF4E、VEGFA和CCND1表达均显著降低,差异有统计学意义(t=9.819、3.508、3.289,P均<0.05);此外,4EGI-1处理组的p-EIF4E蛋白表达水平为(0.33±0.14)%,显著低于对照组(1.02±0.07)%,差异有统计学意义(t=8.818,P=0.0001),同时4EGI-1处理组的VEGFA和CCND1蛋白水平也显著降低(t=5.064、6.334,P均<0.05)。结论EIF4E在卵巢癌肿瘤中高表达。EIF4E抑制剂4EGI-1可能通过调节VEGFA和CCND1的表达发挥作用,因此EIF4E可能成为卵巢癌治疗的潜在靶点。

Objective To investigate the role of eukaryotic initiation factor(EIF)4E in ovarian cancer and its effect on the expression of vascular endothelial growth factor(VEGF)A and cyclin D1(CCND1).Methods SKOV3 ovarian cancer cells were used to analyze the online data to compare the expression differences of EIF4E,VEGFA and CCND1 in ovarian cancer patients and normal sample.The three-dimensional cell culture experiment of EIF4E inhibitor 4EGI-1 was carried out,and the mRNA and protein levels were compared by reverse transcription-polymerase chain reaction(RT-PCR)and Western Blot.Results Cancer genome atlas(TCGA)data showed that the expression levels of VEGFA and CCND1 were significantly increased in ovarian cancer patients,and the differences were statistically significant(both P<0.05).EIF4E was positively correlated with VEGFA and CCND1(both P<0.05).In SKOV3 cells treated with 4EGI-1,the expression of EIF4E,VEGFA and CCND1 were significantly decreased,and the differences were statistically significant(t=9.819,3.508,3.289,all P<0.05).In addition,the expression level of p-EIF4E protein in the 4EGI-1 treatment group was(0.33±0.14)%,which was significantly lower than that in the control group(1.02±0.07)%,and the difference was statistically significant(t=8.818,P=0.0001).At the same time,the levels of VEGFA and CCND1 protein in the 4EGI-1 treatment group were also significantly decreased(t=5.064,6.334,P<0.05).Conclusion EIF4E is highly expressed in ovarian cancer.The EIF4E inhibitor 4EGI-1 May play a role by regulating the expression of VEGFA and CCND1,so EIF4E may be a potential target for ovarian cancer treatment.