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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 investigate the effect of HGFK1 gene on the growth of human prostate xenograft in nude mice. Methods: Human prostate xenograft model was established by injecting human prostate cancer PC-3 cells into the tibial bone marrow of nude mice. PBS was injected into the tail vein of the xenografts and nude mice respectively, carrying HGFK1 gene or enhanced The viral supernatant rAAV-EGFP and rAAV-HGFK1 of adeno-associated virus vector with enhanced green fluorescent protein (EGFP) gene were observed for tumor growth, in vivo metastasis and survival time in nude mice, Ki67, E-cadherin and CD31 expression in tissues. Results: The human prostate cancer xenograft model was successfully established. The tumor volume and quality of rAAV-HGFK1 group were significantly lower than those of PBS and rAAV-EGFP group (P <0.05), and the tumor inhibition rate was 46.69% The median survival time of rats was significantly longer than that of PBS and rAAV-EGFP groups (P <0.05). The incidence of para-aortic lymph node metastasis in PBS and AAV-EGFP groups was higher than that in rAAV-HGFK1 group (P <0.05) The expression of Ki67 and CD31 in tumor tissue was significantly lower than that in PBS and AAV-EGFP group (P <0.05), and the expression of E-cadherin was significantly higher than that in PBS and AAV-EGFP group (P <0.05). Conclusion: HGFK1 can inhibit the growth, metastasis and angiogenesis of human prostate xenografts in nude mice and prolong the survival time of tumor-bearing nude mice.