沉默乏氧诱导因子-1α和生存素基因联合放疗对裸鼠移植人肝癌的抑瘤效应  

Anti-tumor effect of silencing HIF-1α and survivin genes combined with radiotherapy on human hepatoma xenograft in nude mice

作　　者：杨巍[1] 孙婷[2] 曹建平[1] 刘芬菊[1] 朱巍[1] 陈秋[1] 

机构地区：[1]苏州大学放射医学与公共卫生学院放射生物学教研室,苏州215123 [2]苏州大学附属第一医院脑神经研究室,苏州215006

出　　处：《辐射研究与辐射工艺学报》2010年第4期239-244,共6页Journal of Radiation Research and Radiation Processing

基　　金：国家自然科学基金青年项目(30600160)资助

摘　　要：为探讨RNA干扰(RNA interference,RNAi)乏氧诱导因子-1α(Hypoxia induced factor1α,HIF-1α)和生存素(Survivin)基因联合X射线照射对裸鼠移植人肝癌细胞SMMC-7721的抑瘤效应,肿瘤局部注射脂质体包裹的靶向HIF-1α和/或Survivin基因的RNA干扰质粒后,接受5Gy X射线照射。观察各组裸鼠治疗后不同时间肿瘤体积和平均存活时间,以免疫组化染色法检测肿瘤组织Survivin、HIF-1α、增殖细胞核抗原(Proliferation cell nuclear antigen,PCNA)表达和肿瘤间质微血管密度,以TUNEL法检测肝癌细胞凋亡。结果表明,治疗开始后第9-21天,双干扰联合放疗组裸鼠肿瘤体积显著小于单干扰联合放疗组,且平均生存时间明显延长。治疗结束后1天,双干扰联合放疗组裸鼠肿瘤组织Survivin、HIF-1α、PCNA表达和肿瘤间质微血管密度明显低于对照组和放疗组,双干扰联合放疗组移植瘤凋亡细胞百分数较其它组明显升高。结果提示,双干扰联合放疗可有效地抑制裸鼠移植人肝癌细胞增殖和血管生成,促进细胞凋亡,其抑瘤效应明显优于放疗和单干扰联合放疗。In order to investigate the anti-tumor effect of RNA interference silencing HIF-1α and survivin genes combined with X-rays irradiation on human hepatoma xenograft in nude mice,siRNA expression plasmids targeting HIF-1α and/or survivin genes packed by liposome were injected into human hepatoma xenograft which were irradiated with 5 Gy X-rays later. Tumor volumes and mean survival period of mice at different time points were observed. Expression level of HIF-1α,survivin,PCNA and intratumoral microvessel density was detected by Immunohisto-chemical staining respectively. Apoptotic cells in tumor tissue were detected by TUNEL method. The results showed that tumor volumes of pGenesil-survivin-HIF＋5 Gy group were significantly lower than that of pGene-sil-survivin＋5 Gy group and pGenesil-HIF＋5 Gy group on the 9th—21th day after the beginning of therapy. Mean survival period of mice in pGenesil-survivin-HIF＋5 Gy group was the longest. Expression level of HIF-1α,survivin,PCNA and intratumoral microvessel density in pGenesil-survivin-HIF＋5 Gy group were significantly lower than that of the control group and the radiotherapy group on the 1st day after therapy. Percentage of apoptotic cells in tumor tissue in pGenesil-survivin-HIF＋5 Gy group was significantly higher than that in the other groups. These results suggested that RNA interference silencing HIF-1α and survivin genes combined with radiotherapy could effectively inhibit cell proliferation and tumor angiogenesis and enhance apoptosis in tumor xenograft. Its anti-tumor effect was more powerful than that of radiotherapy,RNA interference silencing HIF-1α or survivin gene combined with radiotherapy respectively.

关 键 词：RNA干扰 X射线 乏氧诱导因子-1Α 生存素 肝癌 

分 类 号：R730.54[医药卫生—肿瘤] R735.7[医药卫生—临床医学]