P-GSK3β、P-Akt在卵巢癌中的表达及与卵巢癌耐药关系的研究  

Expression and drug resistance of P - GSK3β,P - Akt in human ovarian cancer

作　　者：魏欣[1] 吕庆杰[1] 孙寒雪[1] 齐亚飞[1] 王劲欧[1] 曹程程[1] 

机构地区：[1]中国医科大学附属盛京医院病理科,辽宁沈阳110004

出　　处：《现代肿瘤医学》2012年第3期584-589,共6页Journal of Modern Oncology

基　　金：辽宁省科学技术计划重大;重点项目(编号:2008225008-6);辽宁省博士启动基金(编号:20041045)

摘　　要：目的:研究磷酸化糖原合酶激酶-3β(P-GSK3β)和磷酸化Akt(P-Akt)蛋白在卵巢上皮癌中的表达情况及其与卵巢癌化疗原发耐药的关系。方法:应用MTT比色分析法检测卵巢癌细胞对紫杉醇(PTX)、表阿霉素(EADM)、顺铂(CDDP)和卡铂(CBP)4种临床常用化疗药物的敏感性。采用免疫组织化学二步法检测10例卵巢上皮良性肿瘤、10例卵巢上皮交界性肿瘤及70例卵巢癌的石蜡包埋组织中P-GSK3β和P-Akt的表达,并分析它们与临床病理因素的关系。结果:65例卵巢癌标本进行体外药敏试验,25例失败,可评价标本为40例。卵巢癌组织中P-GSK3β蛋白的阳性率为57.50%(23/40),P-Akt蛋白的阳性率为65%(26/40),二者呈正相关(r=0.535,P<0.05)。P-GSK3β蛋白表达阳性组和阴性组相比,化疗药物的平均抑制率均显著下降,其中CDDP、PTX两种药物的平均抑制率差异均显著(t=2.573和t=2.174;P=0.014和P=0.036)。P-Akt蛋白表达阳性组和阴性组相比,化疗药物的平均抑制率均显著下降,其中CDDP、CBP两种药物的平均抑制率差异均显著(z=-2.201和z=-2.298;P<0.05和P<0.05)。70例卵巢癌组织中P-GSK3β、P-Akt的阳性表达率分别为60%(42/70)、67.14%(47/70),二者呈正相关(r=0.546,P<0.05);P-GSK3β和P-Akt蛋白在卵巢癌组织组中的表达水平均显著高于卵巢上皮交界性、良性肿瘤,差异有统计学意义,P<0.05,P-GSK3β蛋白的表达与卵巢癌的分化程度及临床分期密切相关,P<0.05,而与卵巢癌的组织学分型无显著相关性。P-Akt与卵巢癌的分化程度密切相关,P<0.05,而与卵巢癌的组织学分型及临床分期无显著相关性。结论:P-GSK3β和P-Akt的过表达在卵巢癌的发展中具有重要的作用,卵巢癌耐药的产生可能与P-Akt结合GSK-3β使其失活有关。Objective：To investigate the expressions of phosphorylated-glycogen synthase kinase-3β（P GSK3β） protein and phosphorylated-Akt（P-Akt） in epithelial ovarian cancer,and to explore the possible relationship between P-GSK3β,P-Akt and drug resistance.Methods：MTT colorimetric assay was performed to measure the sensitivities of 4 anticancer agents commonly used in clinic,including paclitaxel（PTX）,epirubicin（EADM）,carboplatin（CBP）,and cisplatin（CDDP）.The expressions of P-GSK3β,P-Akt protein were detected with immunohistochemical staining 2-step method in specimens from 10 samples of benign epithelial neoplasia,10 cases of borderline epithelial neoplasia and 70 cases of epithelial ovarian cancer,and clinical pathological features was analyzed.Results：Among 65 samples,in vitro drug sensitivity was measurable in 40 samples.The positive expression rates of P-GSK3β and P-Akt in epithelial ovarian carcinoma were 57.50%（23 /40） and 65%（26 /40）,respectively.Positive correlation was found between P-Akt and P-GSK3β（r = 0.535,P 0.05）.Compared with samples with negative expression of P-GSK3β protein,the average inhibition rates of anticancer agents were lower in the samples with positive expression of P-GSK3β protein;the differences in the average inhibition rates of CDDP and PTX were significant（t = 2.573 and t = 2.174;P = 0.014 and P = 0.036）.Compared with samples with negative expression of P Akt protein,the average inhibition rates of anticancer agents were lower in the samples with positive expression of P Akt protein;the differences in the average inhibition rates of CDDP and CBP were significant（z =-2.201 and z = 2.298;P 0.05 and P 0.05）.The positive expression rates of P-GSK3β and P-Akt in 70 epithelial ovarian carcinoma were 60%（42 /70）,67.14%（47 /70）,respectively.Positive correlation was found between P-Akt and P-GSK3β（r = 0.546,P 0.05）.The expression of P-GSK3βand P-Akt in epithelial ovarian cancer group was higher than that in benign and borderline

关 键 词：P-GSK3β P-AKT 卵巢癌 化疗耐药 免疫组织化学 MTT比色分析法 

分 类 号：R737.31[医药卫生—肿瘤]