Metadherin/astrocyte elevated gene-1-based DNA vaccine suppresses progression and metastasis in prostate cancer of mice

2013 
Objective To study the metadherin (MTDH)/astrocyte elevated gene-1 (AEG-1) as targets for gene vaccine inducing immunosuppression mice prostate cancer growth and metastasis of action research.Methods Male C57BL/6 mice (6-8 weekes old) were randomly divided into three groups (n =20),respectively,to phosphate buffered saline (PBS),Pub,Pub-MTDH/AEG-1 attenuated salmonella (1 × 10s cfu) of lavage servo immune; Immune once a week,a total of immune three times.Last one week after the immunization,all in three groups of mice prostate in situ (right and left dorsal lobe) vaccinated 10s RM-1 cell to build orthotopic transplantation tumor model of prostate,induced spontaneous pelvic cavity and retroperitoneal lymph node metastasis; Record each group mice with tumor size,pelvic cavity and retroperitoneal lymph node metastasis number [hematoxylin and eosin (HE) staining shall prevail],CD8 in through immunohistochemical method to detect in situ tumor,the expression of vascular endothelial growth factor (VEGF) and lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1) case,tumor cell apoptosis with TdT-mediated dUTP nick end labeling (TUNEL) method.Results pUb-MTDH/AEG-1 DNA vaccine group compared to the pUb,the PBS group could significantly stimulate CD8 + T cells and cytotoxic T lymphocyte (CTL) response; Effectively inhibit the growth of prostate cancer in situ in mice,MTDH group tumor volume (0.248 ± 0.102) compared with the Pub group (1.475 ± 0.314) (P < 0.01),pelvic cavity and retroperitoneal lymph node metastasis 77.78%,35.7% (P < 0.05) ; Significantly enhanced the expression of CD8 + in the in situ tumor molecular:MTDH group (3.56 ± 0.85),Pub group (5.12 ± 0.90) (P < 0.05),and promote tumor cell apoptosis:MTDH group (39.60 ± 3.28) %,Pub group (16.18 ±2.52)% (P<0.01).Conclusion MTDH/targets AEG-1 gene vaccine in mice prevention immune models,can effectively induce the body specificity immune response,enhance cellular immunity and humoral immunity,inhibit prostate cancer proliferation,invasion,and promote tumor cell apoptosis,extend a tumor-burdened survival time in mice. Key words: Metadherin/astrocyte elevated gene-1 ;  Gene vaccine;  Prostate cancer;  Metastasis
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