›› 2009, Vol. 29 ›› Issue (12): 1419-.

• 论著(基础研究) • 上一篇    下一篇

X连锁凋亡抑制蛋白相关因子-1抑制肝癌裸鼠移植瘤生长的研究

朱黎明1, 涂水平2, 戴 强1, 姚玮艳2, 乔敏敏2, 江石湖2   

  1. 上海交通大学 医学院 1. 第三人民医院消化科, 上海 201900;2. 瑞金医院消化科, 上海 200025
  • 出版日期:2009-12-25 发布日期:2009-12-25
  • 通讯作者: 涂水平, 电子信箱: tushuiping@yahoo.com。
  • 作者简介:朱黎明(1975—), 女, 主治医师, 硕士;电子信箱: sumerrise2006@126.com。
  • 基金资助:

    国家自然科学基金(30572142)

Study on X-linked inhibitor of apoptosis associated factor-1 suppressing xenograft growth in nude mice with hepatocellular carcinoma

ZHU Li-ming1, TU Shui-ping2, DAI Qiang1,YAO Wei-yan2, QIAO Min-min2, JIANG Shi-hu2   

  1. 1. Department of Gastroenterology, The Third People's Hospital, School of Medicine, Shanghai Jiangtong University, Shanghai 201900, China;2. Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China
  • Online:2009-12-25 Published:2009-12-25
  • Supported by:

    National Natural Science Foundation of China, 30572142

摘要:

目的 研究X连锁凋亡抑制蛋白相关因子-1(XAF1)基因对人肝癌裸鼠移植瘤生长的抑制作用。方法 建立人肝癌细胞株SMMC7721裸鼠荷瘤模型,每组5只裸鼠分别在瘤内分3点注射相同感染滴度的重组腺病毒Ad5/F35-XAF1、Ad5/F35-Null对照空病毒及等体积的磷酸缓冲液(PBS),隔天注射1次,疗程2周。每3天测量各组裸鼠移植瘤的体积,观察Ad5/F35-XAF1组移植瘤的生长与其他两组的差异。原位末端标记TUNEL法检测移植瘤细胞的凋亡,免疫组织化学法检测移植瘤中XAF1蛋白表达和微血管密度(MVD)。结果 与PBS组和Ad5/F35-Null组比较,瘤内注射Ad5/F35-XAF1组裸鼠移植瘤体积、质量和MVD显著减小(P<0.05或P<0.01),而移植瘤细胞的凋亡指数和XAF1蛋白的表达率均明显增高(P<0.01)。结论 腺病毒介导XAF1基因可抑制人肝癌裸鼠移植瘤的生长,可能与该基因诱导肝癌细胞凋亡和抑制肿瘤血管形成有关。

关键词: X连锁凋亡抑制蛋白相关因子-1, 肝癌, 腺病毒, 移植瘤, 凋亡, 血管形成

Abstract:

Objective To investigate the inhibitory effect of X-linked inhibitor of apoptosis associated factor-1 (XAF1) on xenograft growth in nude mice with hepatocellular carcinoma. Methods The models of xenografted nude mice with human hepatocellular carcinoma cell line SMMC7721 were established. Intratumor injection was performed on three tumor sites in each group of mice (n=5) with recombinant adenovirus Ad5/F35-XAF1, control virus Ad5/F35-Null at the same infective titre or PBS of the same volume every two days for two weeks. The volumes of xenografts in all nude mice were measured every three days, and the differences between Ad5/F35-XAF1 group and the other two groups were compared. The apoptosis of tumor cells was determined by in situ end-labeling TUNEL method, the expression of XAF1 protein and microvessel density (MVD) were detected by immunohistochemistry. Results Intratumoral injection of Ad5/F35-XAF1 significantly inhibited the growth of tumor xenografts with smaller tumor size, less tumor weight and lower MVD compared with those injected with control virus Ad5/F35-Null and PBS (P<0.05 or P<0.01). However, the apoptosis index and expression of XAF1 protein in Ad5/F35-XAF1 group were significantly increased compared with the other two groups (P<0.01). Conclusion Ad5/F35-XAF1 significantly inhibits xenograft growth in nude mice with hepatocellular carcinoma, which is probably associated with the effects of XAF1 inducing hepatocellular carcinoma cell apoptosis and suppressing tumor angiogenesis.

Key words: X-linked inhibitor of apoptosis-associated factor 1, hepatocellular carcinoma, adenovirus, xenograft, apoptosis, angiogenesis