野生型survivin表达的上调促进胃癌对多西他赛的耐药性  

Elevated expression level of wild-type survivin in gastric cancer promotes in vitro docetaxel-resistance

作　　者：孟化[1] 陆才德[2] 戴德坚[1] 孙玉蕾[3] 谷川允彦 

机构地区：[1]浙江大学医学院附属第二医院外科 [2]宁波大学医学院附属李惠利医院外科 [3]内蒙古医学院附属第一医院妇科 [4]大阪医科大学一般消化器外科

出　　处：《中华医学杂志》2004年第24期2060-2063,共4页National Medical Journal of China

基　　金：国家自然科学基金资助项目(30271483)

摘　　要：目的研究胃癌组织survivin基因各转录变异体表达情况及其与胃癌化疗药物抗药性的关系。方法采用实时荧光定量逆转录聚合酶链反应(RTPCR)技术,对39例胃恶性肿瘤患者肿瘤标本中的survivin转录变异体进行定量检测。采用组织培养肿瘤药敏实验(HDRA)技术,检测胃癌组织对多种化疗药物的敏感性,并且分析该敏感性与survivin转录变异体表达的关系。结果在39例胃癌组织标本中,survivin的表达率100%(39/39),survivin2B的表达率795%(31/39),survivin△Ex3的表达率667%(26/39)。胃癌标本对顺铂、丝裂霉素、5氟尿嘧啶、多西他赛(TXT,商品名泰索帝)和双氟脱氧胞苷在体外实验中的敏感率分别是368%(14/38)、312%(10/32)、231%(9/39)、205%(8/39)和125%(4/32)。泰索帝耐药组中患者野生型survivin的表达水平显著高于泰索帝敏感组(P=0021)。结论研究结果提示野生型survivin的表达促进了胃癌患者对泰索帝的抗药性。Objective To study the expression of three survivin splicing variants in gastric cancer and to evaluate the significant correlation between survivin variants′ expression and chemoresistance in gastric cancer Methods Real time quantitative RT PCR was used to analyze the mRNA expression of survivin variants in 39 gastric tumor specimens resected during operation The clinical resistance to anticancer agents [CDDP, MMC, 5 Fu, docetaxel (TaxotereTXT), and GEM] was analyzed by histocultrure drug response assay (HDRA) Results Among the 39 tumor samples, survivin expression was detected in all tumor samples (39/39); 79 5% (31/39) of the samples demonstrated survivin 2B expression and 66 7% (26/39) of the samples had survivin △Ex3 expression HDRA showed that the in vitro efficacy rates of CDDP, MMC, 5Fu, TXT, and GEM were 36 8%(14/38), 31 2%(10/32), 23 1%(9/39), 20 5%(8/39), and 12 5%(4/32) respectively, equivalent to the previous HDRA studies and historical clinical studies in gastric cancer patients The expression rate of wild type survivin was significantly higher in the group of chemoresistance to TXT than in the group sensitive to docetaxel ( P =0 021). Conclusion Elevated expression level of wild type survivin promotes docetaxel resistance in patients with gastric cancer

关 键 词：多西他赛 泰索帝 胃癌组织 表达率 SURVIVIN表达 化疗药物 患者 野生型 变异体 抗药性 

分 类 号：R735.2[医药卫生—肿瘤]