Effect on Pancreatic Carcinoma Tumogenicity and its Metastasis by Tumorself Vaccine Encoded by Adenoviral Mediated Gene Transfer of SLC in Nude Mice / 医学研究杂志

ABSTRACT

Objective To evaluate the enhancement effect of SLC(secondary lymphoid tissue chemokine)gene mediated by a repli- cation 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-dimethyhhiazol-2-yl]-2,5-diphenyhetrazolium bromide)assay was used to estimate the proliferation of ASPC-1 cells;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 re- vealed by CD34 immunohistochemical staining was measured and TIL in tumor region was also evaluated.Results Growth and tube forma- tion of ASPC-1 cells infected with Ad-SLC were suppressed significantly compared with cells 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 mem- brane 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 cells,attracting TIL to tumor region and angiogenesis may account for its effect.