P-糖蛋白、多药耐药相关蛋白在胃癌的表达与化疗敏感性的相关性研究  

Expressions of P-glycoprotein and multidrug resistance-associated protein correlate with chemosensitivity in vitro in gastric cancer

作　　者：许洪伟[1] 丛衍群[1] 王万忠[2] 姜军梅[1] 秦成坤[3] 秦成勇[1] 

机构地区：[1]山东大学山东省立医院消化内科,山东济南250021 [2]山东大学山东省立医院病理科,山东济南250021 [3]山东大学山东省立医院普外科,山东济南250021

出　　处：《山东大学学报（医学版）》2005年第7期594-597,601,共5页Journal of Shandong University:Health Sciences

基　　金：山东省卫生厅科研基金资助课题(2001CA2DBB2)。

摘　　要：目的:探讨胃癌组织中P-糖蛋白(P-glycoprotein,P-gp)、多药耐药相关蛋白(multidrugresis-tance-associatedprotein,MRP)的表达及对胃癌原代细胞培养体外化疗药物敏感性的影响。方法:应用免疫组化法检测P-gp及MRP在48例胃癌及癌旁组织的表达,同时通过胃癌原代细胞培养MTT药敏试验,检测胃癌对7种临床常用化疗药物的敏感性及耐药性,进一步分析药敏试验结果与P-gp、MRP表达的相关性。结果:在48例胃癌中,P-gp及MRP阳性率分别为41.7%、29.2%,共同表达率为25.0%。癌旁组织与癌组织的P-gp、MRP阳性表达率无显著差异。在顺铂(DDP)、丝裂霉素(MMC)、阿霉素(ADM)、鬼臼乙叉甙(VP-16)、5-氟尿嘧啶(5-FU)、羟基喜树碱(HCPT)、甲氨蝶呤(MTX)中,ADM、VP-16、HCPT耐药组P-gp、MRP阳性表达及共表达率较敏感组显著升高。结论:胃癌组织P-gp、MRP表达可导致胃癌原发性耐药。P-gp、MRP介导的MDR是ADM、VP-16、HCPT耐药的重要因素。Objective： To explore the expressions of P-glycoprotein （P-gp） and multidrug resistance-associated protein （MRP） in tissues of gastric cancers and their effect on chemosensitivity of gastric cancer cells cultured primarily to adriamycin （ADM）, mitomycin-C （MMC）, 5-fluorouracil （5-FU）, cisplatin （DDP）, etoposide（VP-16）, methotrexate（MTX）, 10-hydroxycampothecine（HCPT）. Methods： The expressions of P-gp and MRP in 48 cases of paraffin embedded gastric cancer tissues were detected immunohistochemically used monoclonal antibodies. The chemosensitivity of the gastric cancer tissues to the seven antitumor agents obtained by MTT assay through primary cultured cells from excised specimens were examined. Results： The positive rate of P-gp and MRP was 41.7% and 29.2%, respectively, and the coexpression rate was 25.0%. There were no significant difference of expression rate and strength in cancer tissue and adjacent tissue. Of the seven antitumor agents, ADM, VP-16, and HCPT had significantly increased expression rates of P-gp, MRP, as well as their coexpression rates than chemosensitivity ones. Conclusions： The positive expression of P-gp and MRP can result in primary chemoresistance. The MDR mediated by P-gp and MRP is an important factor for chemoresistance of ADM, VP-16, and HCPT.

关 键 词：胃肿瘤 P-糖蛋白 多药耐药相关蛋白质类 化疗敏感性 免疫组织化学 

分 类 号：R735.2[医药卫生—肿瘤] R392.11[医药卫生—临床医学]