HGF基因转染对裸鼠人淋巴瘤移植瘤的促进作用

Effect of HGF gene transfection on human lymphoma xenografts in nude mice

目的:探讨肝细胞生长因子(HGF)基因转染对裸鼠人淋巴瘤移植瘤的促进作用及其机制。方法:采用HGF基因重组质粒pVITRO2-HGF转染的Raji细胞建立裸鼠皮下人淋巴瘤移植瘤模型,动态监测裸鼠体重和肿瘤大小;8周后获取瘤组织,分别采用脱氧核糖核酸末端转移酶介导的缺口末端标记技术(TUNEL)和免疫组化检测移植瘤组织的细胞凋亡和微血管密度(MVD),并进行相关分析。结果:造模成功率为96.7%。HGF转染组的瘤体积明显大于HGF转染+VP-16组(P<0.01)、未转染组与空载体组(P<0.01),HGF转染+VP-16组也大于对照组(P<0.01),未转染组与空载体组间无显著差异(P>0.05)。pVITRO2-HGF转染组凋亡指数显著低于对照组(P<0.01),经VP-16诱导后凋亡增加(P<0.01),但仍低于对照组(P<0.01)。pVITRO2-HGF转染组的MVD显著高于对照组(P<0.01),但经VP-16诱导后血管增生降低(P<0.01),但仍高于对照组(P<0.05),对照组间无显著差异(P>0.05)。结论:HGF基因转染可显著促进裸鼠人淋巴瘤移植瘤的生长,明显抑制凋亡的发生,这一效应可能与其促进肿瘤血管新生和抑制肿瘤细胞凋亡有关。

AIM： To explore the promotion effect of hepatocyte growth factor （HGF） gene transfection on hu- man lymphoma xenografts in nude mice. METHODS： The model of human lymphoma xenograft in nude mice was estab- lished by transplantation of Raji ceils, which were transfected with recombinant plasmid pVITRO：HGF harboring the HGF gene. The body weight of the nude mice and the tumor size were dynamically monitored and the tumor tissues were obtained after 8 weeks. Additionally, the methods of terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） and immunohistochemistry were used to detect the apoptotic index （AI） and microvessel density （MVD）. RESULTS： The success rate of the human lymphoma xenografts in nude mice was 96.7 %. The tumor volume in HGF transfection group was significantly greater than that in HGF transfection ＋ VP-16 group and control groups （ non-transfection group and empty vec- tor group）. The tumor volume in HGF transfection ＋ VP-16 group was also bigger than that in control groups. No difference of the tumor volume between non-transfection group and empty vector group was observed. AI in HGF transfection group was substantially lower than that in control groups. AI in HGF transfection ＋ VP-16 group showed a little higher than that in HGF transfection group, yet was still lower than that in control groups. MVD in HGF transfection group was extraordinary higher than that in control groups, but decreased after VP-16 induction （P 〈 0.01 ）, which was still higher than that in control groups. CONCLUSION： HGF gene transfection significantly promotes the growth of human lymphoma xenografts in nude mice and substantially inhibits the apoptosis presumably owing to promoting tumor angiogenesis and inhibiting tumor cell apoptosis.