腺相关病毒介导的肝细胞生长因子Kringle 1结构域对人前列腺癌裸鼠骨移植瘤生长的影响

Effect of adenovirus-associated virus carrying kringle 1 domain of hepatocyte growth factor gene on the growth of human prostatic carcinoma xenograft in nude mouse bone

目的:探讨肝细胞生长因子Kringle1结构域(kringle1domain of hepatocyte growth factor,HGFK1)基因对人前列腺癌裸鼠骨移植瘤生长的影响。方法:通过向裸鼠胫骨骨髓腔内注射人前列腺癌PC-3细胞,建立人前列腺癌裸鼠骨移植瘤模型;分别向移植瘤和裸鼠尾静脉内注射PBS、携带有HGFK1基因或增强型绿色萤光蛋白(enhanced green fluorescent protein,EGFP)基因的腺相关病毒载体的病毒上清液rAAV-EGFP和rAAV-HGFK1,观察肿瘤生长、体内转移和裸鼠生存时间,免疫组织化学法检查移植瘤组织中Ki67、E-cadherin和CD31的表达。结果:成功建立了人前列腺癌裸鼠骨移植瘤模型,rAAV-HGFK1组的肿瘤体积和质量明显小于PBS和rAAV-EGFP组(P<0.05),抑瘤率达46.69%;rAAV-HGFK1组裸鼠的中位生存时间比PBS和rAAV-EGFP组明显延长(P<0.05);PBS和AAV-EGFP组腹主动脉旁淋巴结转移发生率高于rAAV-HGFK1组(P<0.05);rAAV-HGFK1组肿瘤组织中Ki67和CD31的表达明显低于PBS和AAV-EGFP组(P<0.05),E-cadherin的表达明显高于PBS和AAV-EGFP组(P<0.05)。结论:HGFK1具有抑制人前列腺癌裸鼠骨移植瘤生长、转移和血管生成的作用,并可延长荷瘤裸鼠的生存时间。

Objective： To observe the effect of adenovirus-associated virus carrying kringle 1 domain of hepatocyte growth factor （HGFK1） gene on the growth of human prostatic carcinoma xenograft in nude mouse bone. Methods： The human prostatic carcinoma xenograft in nude mouse bone was established by injection of PC-3 cells into the mouse tibial bone marrow cavity. PBS or the supernatant of recombinant adenovirus-associated virus carrying enhanced green fluorescent protein （EGFP） gene （rAAV-EGFP） or HGFK1 gene （rAAV-HGFK1） was injected into the prostatic carcinoma bone xenograft or into the tail vein. Tumor growth, metastasis and the survival of nude mice were observed. The expression levels of Ki67, E-cadherin and CD31 in the bone xenograft were detected by immunohistochemistry. Results： The human prostatic carcinoma xenograft in nude mouse bone was successfully established. The tumor volume was smaller and the tumor weight was lower in the rAAV-HGFK1 group than those in the PBS group and the rAAV-EGFP group （P〈0.05）. The tumor growth inhibition rate in the rAAV-HGFK1 group was 46.69%. The median survival of nude mice in the rAAV-HGFK1 group was longer than those in the PBS group and the rAAV-EGFP group （P〈0.05）. The paraaortic lymph node metastasis rates in the PBS group and the rAAV- EGFP group were higher than that in the rAAV-HGFK1 qrouD （P〈0.05）. The expression levels of Ki67and CD31 were lower and the expression level of E-cadherin was higher in the rAAV-HGFK1 group than those in the PBS group and the rAAV-EGFP group （P〈0.05）. Conclusion： HGFKI can inhibite the growth, metastasis and angiogenesis of human prostatic carcinoma bone xenograft in nude mice, as well as prolong the survival of nude mice.