胃、大肠癌COX-2和多药耐药相关因子表达与体外化疗药敏性的关系及意义

目的 探讨胃、大肠癌细胞环氧合酶-2(COX-2)、多药耐药相关因子(P-gp、GST-π,TopoⅡα)表达与体外化疗药敏性的关系及临床意义.方法 84例胃癌、大肠癌标本采用免疫组化染色法检测COX-2、P-gp、GST-π、TopoⅡα的表达,进行MTT法体外化疗药物敏感性实验,分析4种因子表达与9种化疗药物对肿瘤细胞抑制率的关系.结果 肿瘤COX-2、P-gp、GST-π、TopoⅡα强表达率分别为48.8%、76.2%、78.6%、66.7%;COX-2与P-gp、COX-2与TopoⅡα之间表达具有正相关性(r=0.287,0.256,P均＜0.05).在各因子表达程度与药物对肿瘤细胞抑制率的关系中,COX-2强表达时,紫杉醇(PTX)、表阿霉素(eADM)、羟基喜树碱(OPT)对肿瘤细胞的抑制率降低(t=2.21、3.11、2.09;P均＜0.05);P-gp强表达组PTX、奥沙利铂(OXA)、顺铂(DDP)对肿瘤细胞的抑制率低于弱表达组(t=2.54、2.47、2.05,P均＜0.05),GST-π强表达与5-氟尿嘧啶(5-Fu)对肿瘤细胞的抑制率降低有关(t=2.13,P＜0.05),TopoⅡα强表达时,长春新碱(VCR)、PTX、eADM对肿瘤细胞的抑制率升高(t=-2.29、-2.12、-2.26;P均＜0.05).结论 COX-2在胃、大肠癌多药耐药中起一定的作用;COX-2、P-gp、GST-π、TopoⅡα各自表达程度仅与部分化疗药物耐药性有关;胃、大肠癌对化疗药物的耐药性与多种机制有关,仅检测部分多药耐药相关因子的表达不能准确预测化疗药敏性.

Relationship of Cyclooxygenase-2 and Multidrug Resistance Associated Factors to Chemosensitivities in Gastrointestinal Carcinomas

Objective To investigate the relationship of cyclooxygenase-2(COX-2),p-glycoprotein(P-gp),glutathione S-transferase-πCGST-π),and topoisomerase Ⅱα(TopoⅡα)to chemosensitivities in gastrointestinal tract carcinomas.Methods The tumor tissue samples were collected from 84 specimens of gastrointestinal carcinomas.The expressions of COX-2,P-gp,GST-π,and Topo Ⅱα were determined immunohistochemically.The chemosenisitivity of each sample to 9 drugs were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Results The positive rates of COX-2,P-gp,GST-π and Topo Ⅱα were 48.8%,76.2%,78.6%and 66.7%respectively.The expression of COX-2 was correlated with the expression of P-gp and Topo Ⅱα significantly(r=0.287,0.256,both P＜0.05).In terms of relationships of four MDR-related factors expression to inhibition rate of tumor cells,the inhibition rates of PTX,eADM and OPT in COX-2 strong expression group were significantly lower than those in COX-2 weak expression group(t=2.21,3.11,2.09;all P＜0.05).The inhibition rates of PTX,OXA and DDP in P-gp strong expression group were lower than those in weak group 0=2.54,2.47,2.05;all P＜0.05).There were lower inhibition rates for 5-Fu in GST-π strong expression group(t=2.13,P＜0.05),and higher inhibition rates for VCR,PTX and eADM in TopoⅡα strong expression group(t=-2.29,-2.12,-2.26;all P＜0.05).Conclusions The overexpressions of MDR-related factors in gastrointestinal carcinomas were only associated with the chemosensitivity to some of the chemotherapeutic agents,but not all.MDR related factors may be not specific and accurate predictors for the clinical chemosensitivity.