【摘 要】
：
目的 研究杆状病毒凋亡抑制重复含体6 (BIRC6)在肝细胞肝癌中的表达,其与临床病理特征和预后的关系,探讨其在肝癌发生中的作用及其分子生物学机制.方法 采用免疫印迹法检测BIRC6在7种肝癌细胞和1种永生化肝细胞中的表达,免疫组织化学法检测其在160例肝癌组织和相应癌旁组织中的表达.计量资料行t检验,BIRC6表达与临床病理特征的相关性行x2检验,生存分析行乘积极限法.采用慢病毒介导的BIRC6
【机 构】
：
200032 上海,复旦大学附属中山医院消化内科,上海市肝病研究所 复旦大学上海医学院,分子病毒学
【出 处】
：
The 14th Congress of Gastroenterology China(第十四届全国消化系病学术会议)
论文部分内容阅读
目的 研究杆状病毒凋亡抑制重复含体6 (BIRC6)在肝细胞肝癌中的表达,其与临床病理特征和预后的关系,探讨其在肝癌发生中的作用及其分子生物学机制.方法 采用免疫印迹法检测BIRC6在7种肝癌细胞和1种永生化肝细胞中的表达,免疫组织化学法检测其在160例肝癌组织和相应癌旁组织中的表达.计量资料行t检验,BIRC6表达与临床病理特征的相关性行x2检验,生存分析行乘积极限法.采用慢病毒介导的BIRC6基因沉默方法进行体外细胞增殖、周期和凋亡实验,并构建体内裸鼠成瘤模型,以研究其肿瘤生物学行为.采用聚合酶链反应和免疫印迹法检测BIRC6基因沉默后p53的表达,采用免疫荧光、免疫共沉淀和泛素化实验探讨二者的相互作用,并以核酸干扰法沉默p53,观察其对BIRC6基因沉默所致生物学效应的影响.结果 BIRC6在肝癌细胞中的表达显著高于肝细胞,在肝癌组织中的表达明显高于癌旁组织,且与ALT、血管侵袭相关.癌组织中BIRC6表达较高的患者预后较差.体外BIRC6沉默显著抑制了细胞增殖,致使G1/S期阻滞,并增强了肝癌细胞对于索拉菲尼诱导的凋亡的敏感性.体内裸鼠成瘤研究结果显示,BIRC6敲除抑制移植瘤的生长并增强了裸鼠体内肿瘤细胞对于索拉菲尼的敏感性.相关机制研究表明BIRC6与p53之间存在相互作用,BIRC6通过促进p53泛素化而促使其降解.体外靶向干扰p53后,BIRC6沉默所致的细胞增殖抑制、G1/S期阻滞及其对索拉菲尼敏感性的增强效应在很大程度上得到逆转.结论 癌基因BIRC6在肝癌发生中发挥调节细胞增殖、细胞周期和凋亡的多重效应,且这种效应高度依赖于p53.BIRC6与下游p53之间存在相互作用,BIRC6通过促进p53的泛素化而促使其降解.同时,BIRC6基因沉默所致的p53激活与索拉菲尼治疗对于多激酶通路的抑制有协同效应.BIRC6是一个判断肝癌预后的新型生物学指标和基因治疗的新靶点.
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