Akt基因在上皮性卵巢癌组织中的表达及临床意义  

The expression and clinical significance of Akt in human epithelium ovarian cancer

作　　者：张海燕[1] 孙红[1] 

机构地区：[1]复旦大学附属妇产科医院,上海200011

出　　处：《现代妇产科进展》2014年第12期964-967,共4页Progress in Obstetrics and Gynecology

基　　金：上海科委医学引导项目(No:10411960800);国家自然基金(No:81001150)

摘　　要：目的:检测Akt基因在正常卵巢组织、上皮性卵巢囊肿、交界性上皮性卵巢肿瘤和上皮性卵巢癌组织中的表达水平,探讨其在上皮性卵巢癌演变过程中的作用及临床意义。方法:收集正常卵巢组织10例、良性上皮性卵巢囊肿组织15例、交界性上皮性卵巢肿瘤组织15例和上皮性卵巢癌组织40例。RT-PCR和Western blot法分别检测Akt mRNA和蛋白的表达水平,并分析其与临床病理特征的相关性。采用Akt激酶特异性抑制剂Triciribine分别作用于上皮性卵巢癌SKOV3、ES-2细胞,MTT法和FCM分别检测细胞增殖和凋亡,比较单独抑制剂Triciribine、单独顺铂及联合两种制剂的治疗方案对SKOV3、ES-2细胞的作用。结果:(1)Akt1、Akt2、Akt3 mRNA及p-Akt在正常卵巢组织、上皮性卵巢囊肿、交界性上皮性卵巢肿瘤和上皮性卵巢癌组织中均有表达,上皮性卵巢癌组织中的表达水平显著高于其余3组(P<0.05);(2)p-Akt表达水平、总Akt mRNA水平与上皮性卵巢癌的临床分期和组织分级有关(P<0.05),而与患者年龄和病理类型无关(P>0.05);(3)Triciribine能有效抑制SKOV3、ES-2细胞中p-Akt水平,呈浓度依赖性抑制癌细胞生长率,联合顺铂处理可增加癌细胞的凋亡率。结论:Akt在上皮性卵巢癌组织过度激活,与临床分期和组织分级相关。Akt异常激活不仅是上游PI3K异常激活的后续效应,同时与Akt自身扩增密切相关。Triciribine阻断Akt的信号传导可增强顺铂化疗的疗效。Objective：To explore the expression and significance of Akt at protein and mRNA levels in epithelial ovarian cancer tissues. Methods：The expression of Akt at protein and mRNA levels were evaluated by Western blot and RT-PCR in normal ovarian epithelium （ group N, n = 10）, benign epithelial ovarian tumor tissues（ group B1, n = 15 ）, borderline epithelial ovarian tumor tissues （ group B2, n = 15 ） and epithelial ovarian cancer tissues （ group E, n = 40）. The relevant clinical pathological parameters were analyzed. Western blot detected the effect of Ticiribine in SKOV3 and ES-2 cells. Methyl thiazolyl tetrazolium and flow cytometry were used to detect the growth rate and early apoptosis rate after cisplatin-based chemotherapy, Triciribine or combination treatment, respectively. Results： The tendency of two methods was coincidence on the whole. Overexpression of Akts isoforms and overactivation of Akt were detected in group E, compared with group N, group B1, and group B2 （P〈0. 05 ）. Significant differences were noted between Akt activation, clinical staging and tumor differentiation degree（P〈0.05）.There was no significant relationship between Akt activation and age at surgery or pamologlcal type （P〉0.05）. The activation of Akt was dramatically inhibited after exposured to 10μmol/L Trieiribine under normal culture condition （ P 〈 0.05 ）. Triciribine enhanced the sensitivity of cisplatin-based chemotherapy in SKOV3 and ES-2 cell. Conclusions： Overactivation of PI3K/ Akt signaling existed in late epithelial ovarian cancer tissues. The alteration of Akts were correlated with clinicopathological stage and tumor differentiation degree. Triciribine could enhance cisplatin-based chemotherapy in epithelial ovarian cancer cells by inhibiting phospho-Akt level.

关 键 词：上皮性卵巢癌 AKT 信号通路 Triciribine 

分 类 号：R737.3[医药卫生—肿瘤]