COX-2选择性抑制剂塞来昔布联合PPAR-γ配体罗格列酮治疗子宫内膜癌的实验研究  

Inhibiting Effect of Selective COX-2 Inhibitor Celecoxib Combined with PPAR-γ Ligand Rosiglitazone on Endometrial Carcinoma

作　　者：冯振中[1] 武世伍[1] 李楠[1] 蔡兆根[1] 吕秀红[2] 陈嘉薇[2] 

机构地区：[1]蚌埠医学院第一附属医院病理科,蚌埠医学院病理学教研室,安徽省感染与免疫重点实验室 [2]上海交通大学附属上海市第一人民医院病理科,蚌埠233004

出　　处：《华中科技大学学报（医学版）》2014年第6期619-625,共7页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：安徽省自然科学基金资助项目(No.1208085MH152);安徽省教育厅自然科学基金重点资助项目(No.KJ2014A160)

摘　　要：目的研究环氧合酶-2(COX-2)和过氧化物酶体增殖物激活受体-γ(PPAR-γ)蛋白在子宫内膜癌中的表达和临床意义,探讨COX-2选择性抑制剂塞来昔布联合PPAR-γ配体罗格列酮共同应用对于肿瘤细胞的干预效果。方法采用免疫组化方法,结合组织芯片技术,检测124例子宫内膜样腺癌、35例正常子宫内膜中COX-2和PPAR-γ蛋白的表达水平,结合临床病理因素进行分析。联合应用塞来昔布和罗格列酮处理RL95-2子宫内膜癌细胞,观察其对于肿瘤细胞生物学行为的影响和协同抑瘤作用。结果在子宫内膜样腺癌中,COX-2蛋白表达明显升高,PPAR-γ蛋白表达相对降低,两者具有负性相关关系。塞来昔布和罗格列酮可以有效抑制RL95-2子宫内膜癌细胞的增殖、侵袭、转移能力,联合应用抑制肿瘤的效果明显高于单独药物组。结论 COX-2的高表达和PPAR-γ的低表达与子宫内膜癌的发生、发展有密切关系,以COX-2和PPAR-γ为共同靶点,有望成为临床子宫内膜癌预防和治疗的重要手段和有效途径。Objective To investigate the expression and clinical significance of COX‐2 and PPAR‐γin endometrial carcino‐ma （EEC） ,and to determine whether celecoxib combined with rosiglitazone ,a specific PPAR‐γ ligand ,synergistically inhibited growth ,invasion and metastasis of EEC cells.Methods Tissue microarray （TMA） and immunohistochemical staining were em‐ployed to detect the expression of COX‐2 and PPAR‐γ in EEC cells of 124 cases ,and normal endometrium samples （n=35） . Subsequently ,we examined the effects of celecoxib and rosiglitazone on the cell proliferation ,invasion and migration in endome‐trial carcinoma cell line RL95‐2.Results The expression of COX‐2 and PPAR‐γ protein was significantly increased and de‐creased ,respectively.Statistical analysis confirmed a significant negative relationship between COX‐2 and PPAR‐γ in EEC.Celecoxib and rosiglitazone inhibited proliferation ,invasion and migration of RL95‐2 cells.Moreover ,the inhibition effect was higher in the combination group than that in celecoxib or rosiglitazone alone group.Conclusion These data showed that up‐regulation of COX‐2 and down‐regulation of PPAR‐γmay play a crucial role in EEC development ,hence ,these markers may be used as novel therapeutic targets in patients with EEC.

关 键 词：子宫内膜癌 环氧合酶-2 过氧化物酶体增殖物激活受体-Γ 塞来昔布 罗格列酮 

分 类 号：R737.33[医药卫生—肿瘤]