【摘要】 背景与目的:目前肿瘤化疗疗效尚不理想,通过预测个体肿瘤对化疗药物的敏感性来指导临床治疗,有可能提高化疗疗效。本研究通过三维培养药敏实验测定结直肠癌的药物敏感性,并分析与肿瘤组织多药耐药基因表达产物水平的关系。方法:应用三维培养体外药敏实验技术,检测表阿霉素、顺铂、草酸铂、氟尿嘧啶(5-fluorouracil,5-FU)、泰素帝、伊立替康6种单药和5-FU+表阿霉素+顺铂、5-FU+伊立替康、5-FU+草酸铂、5-FU+泰素帝+顺铂4组联合用药对22例结直肠癌组织的抑制率,抑制率大于30%定义为敏感,计算敏感率。应用逆转录聚合酶链反应和免疫组化法测定结直肠癌组织中MDR1、MRP1、ABCG2基因蛋白表达水平;用Spearman相关分析法分析肿瘤药物敏感性和多药耐药蛋白表达的相关性。结果:单药组抑制率最高为草酸铂(17.5%),敏感率最高为5-FU(36.4%);联合用药组抑制率最高为5-FU+草酸铂(54.1%),敏感率最高为5-FU+表阿霉素+顺铂(71.4%)和5-FU+泰素帝+顺铂(71.4%);联合用药组抑制率和敏感率均高于单药组(P<0.05)。MDR1、MRP1、ABCG2mRNA的阳性率分别为88.9%、55.6%、55.6%;MDR1、MRP1、ABCG2蛋白的阳性率分别为55.6%、33.3%、50.0%;多药耐药基因MDR1、MRP1、ABCG2mRNA和蛋白的表达无相关性(P>0.05)。ABCG2蛋白高表达与结直肠癌对表阿霉素的耐药有相关性(P<0.05)。结论:结直肠癌多药耐药蛋白表达与肿瘤药物敏感性有一定相关性;结合三维培养药敏实验和多药耐药基因表达产物水平检测,有可能对个体肿瘤的化疗敏感性进行预测,筛选化疗敏感药物。更多还原

【Abstract】 Background and Objective:The therapeutic effects of chemotherapy for malignant neoplasms are still unsatisfactory.This study was to evaluate the chemosensitivity of colorectal cancer tissues to therapeutic agents using histoculture drug response assay(HDRA), and explore the correlation of chemosensitivity to the expression levels of multidrug resistance(MDR) genes and proteins.Methods:Twenty-two specimens of colorectal cancer were collected.The inhibition rates of single agents, including epirubicin, cisplatin(DDP), oxaliplatin, 5-FU, taxetere, irinotecan, and combinations of these agents, including 5-FU +epirubicin +DDP, 5-FU + irinotecan, 5-FU+oxaliplatin, 5-FU+taxetere+ DDP on colorectal cancer tissues were evaluated by HDRA.The agent whose inhibition rate was greater than 30% was considered sensitive, and the sensitivity was calculated.mRNA and protein levels of MDR genes and proteins in colorectal cancer tissues were measured by RT-PCR and immunohistochemistry.Results:Among the single agents, the inhibition rate of oxaliplatin(17.5%) and sensitivity of cancer tissues to 5-FU(36.4%) were the highest.In the combination groups of agents, the inhibition rate of 5-FU + oxaliplatin(54.1% ), and sensitivity of cancer tissues to 5-FU+epirubicin+DDP(71.4%) and to 5-FU+taxetere+DDP(71.4%) were the highest.The inhibition rates of and sensitivity of cancer tissues to combined agents were higher than those of single agents(P <0.05).Expressions of MDR1, multidrug resistance protein-1(MRP1), ABC-binding cassette transporter superfamily-G-2(ABCG2) mRNA were detected in 88.9%, 55.6% and 55.6% of specimens respectively;while those of MDR1, MRP1 and ABCG2 proteins were detected in 55.6%, 33.3%, and 50.0% of specimens respectively.Expressions of mRNA and proteins had no correlation in MDR1, MRP1 and ABCG2(P >0.05).High expression of ABCG2 protein was correlated to the resistance of colorectal cancer cells to epirubicin(P<0.05).Conclusions:Expressions of MDR proteins are correlated to chemosensitivity of colorectal cancer to some extents.By combining HDRA with measurement of MDR genes and proteins, chemosensitivity of individual tumors may be predicted to guide selection of effective chemotherapeutic agents.更多还原