CAJ | 학술논문

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。
목적：연구배양합매‐2（COX‐2）화과양화물매체증식물격활수체‐γ（PPAR‐γ）단백재자궁내막암중적표체화림상의의，탐토COX‐2선택성억제제새래석포연합PPAR‐γ배체라격렬동공동응용대우종류세포적간예효과。방법채용면역조화방법，결합조직심편기술，검측124례자궁내막양선암、35례정상자궁내막중COX‐2화PPAR‐γ단백적표체수평，결합림상병리인소진행분석。연합응용새래석포화라격렬동처리RL95‐2자궁내막암세포，관찰기대우종류세포생물학행위적영향화협동억류작용。결과재자궁내막양선암중，COX‐2단백표체명현승고，PPAR‐γ단백표체상대강저，량자구유부성상관관계。새래석포화라격렬동가이유효억제RL95‐2자궁내막암세포적증식、침습、전이능력，연합응용억제종류적효과명현고우단독약물조。결론 COX‐2적고표체화PPAR‐γ적저표체여자궁내막암적발생、발전유밀절관계，이COX‐2화PPAR‐γ위공동파점，유망성위림상자궁내막암예방화치료적중요수단화유효도경。
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.