转SLC基因转染胰腺癌疫苗对裸鼠成瘤性及淋巴转移的影响  

Effect on Pancreatic Carcinoma Tumogenicity and its Metastasis by Tumorself Vaccine Encoded by Adenoviral Mediated Gene Transfer of SLC in Nude Mice.

作　　者：封光华[1] 贾忠[1] 朱玮[1] 罗中尧[1] 贺冠海[1] 蔡阳[1] 谢琦[1] 

机构地区：[1]浙江省杭州市第一人民医院普外科,310006

出　　处：《医学研究杂志》2006年第10期26-29,共4页Journal of Medical Research

基　　金：杭州市卫生局重点项目资助

摘　　要：目的评价重组腺病毒介导的转次级淋巴组织趋花因子(secondarylymphoid tissue chemokine,SLC)基因自体肿瘤疫苗对活体胰腺癌的抑制作用,并探讨SLC的作用机制。方法将人胰腺癌细胞株ASPC1,转染SLC基因。用MTT法评估ASPC1细胞的增生情况,用绒毛膜尿囊膜法评估其在活体和试管中的血管发生,并将转SLC基因的胰腺癌细胞灭活后种植于裸鼠胰腺癌模型观察其肿瘤生长抑制情况,用CD34免疫组化染色法测量微血管密度,用CD4、CD8免疫组化染色测量肿瘤浸润淋巴细胞。结果转染SLC基因的ASPC1细胞的生长和管道生成与未转染SLC和生理盐水处理相比被明显抑制,绒毛膜尿囊膜法结果显示转SLC基因组的新血管生成少于未转染SLC组和生理盐水组。转染SLC基因组的肿瘤体积少于未转染SLC组和生理盐水组,转染SLC基因组的微血管密度亦少于未转染组和生理盐水组,而肿瘤内浸润淋巴细胞转SLC基因组显著增多。结论腺病毒介导的转SLC基因自体肿瘤疫苗对治疗胰腺肿瘤有效。其作用机制可能与SLC抑制血管内皮细胞的生长和血管发生以及吸引免疫效应细胞有关。Objective To evaluate the enhancement effect of SLC （secondary lymphoid tissue chemokine） gene mediated by a replication deficient recombinant adenovirus （Ad） on human pancreatic cancer in vitro and vivo and to investigate the mechanism of action of SLC. Methods Human pancreatic carcinoma cell line ASPC - 1 was infected with Ad - SLC and Ad - CFG,and compared with phosphate buffered saline （ PBS）. MTT （3, - [4,5 - dimethylthiazol - 2 - yt] - 2,5 - diphenyltetrazolium bromide） assay was used to estimate the proliferation of ASPC - 1 ceils ; tube formation assay and choriallantoic membrane assay were used to evaluate angiogenesis in vivo and in vitro. Xenografted nude mice with pancreatic cancer were established to observe in vivo tumour growth suppression. Microvessel density revealed by CD34 immunohistochemical staining was measured and TIL in tumor region was also evaluated. Results Growth and tube formation of ASPC - 1 ceils infected with Ad - SLC were suppressed significantly compared with ceils infected with Ad - CFG or ceils treated with PBS. Neovascularisation in the Ad - SLC group was less than that in the PBS and Ad - CFG groups,based on chorioallantoic membrane results. Volumes of pancreatic tumours in the Ad - SLC group were significantly smaller than those in the PBS and Ad - CFG groups at the end of the treatment period. Microvessel density in the Ad - SLC group was significantly lower than that in the Ad - CFG and PBS groups and TILs in tumor region in the Ad - SLC group was significantly risen much more than that in the Ad - CFG and PBS groups when the mice transferd the same number of TILs from spleen of health mice. Conclusions The SLC gene mediated by adenovirus is efficient for gene therapy for pancreatic carcinoma. Suppression of SLC on proliferation of vascular endothelium ceils , attracting TIL to tumor region and angiogenesis may account for its effect.

关 键 词：胰腺癌 自体肿瘤疫苗 SLC 

分 类 号：R735.9[医药卫生—肿瘤]