MTDH/AEG-1-based DNA Vaccine Suppresses Progression And Enhances Chemosensitivity To Paclitaxel In Prostate Cancer

Objective:(1), through the experiments to evaluation to MTDH/AEG-1for the genevaccine targets on the mice immune functions influence.(2), through the bodydiscussed in the experiment MTDH/AEG-1for the target genes in mice vaccine ofprostate cancer growth transfer and enhance the role of chemotherapy drug paclitaxelsensitivity.Methods: Through the flow cytometric detection immune mice, the spleen CD4+and CD8+T cells subsets and using CytoTox96as Radioactive Cytotoxicity Assaytest kit Cytotoxicity T lymphocytes (CTL) reaction. The immune preventive model:will the little black male C57BL/6rat (6to8weeks old) randomly divided into threegroup (n=8), were given PBS, contains Pub-MTDH, Pub subtraction salmonella (10~8cfu) irrigation stomach servo immune; Between a week immune once total immunethree times. The last time a week after the immune, all in the three groups of mice insitu in the prostatic (left, right back and sides of the leaves) to vaccinate10~5RM-1cells to construct the in situ tumor model prostate transplantation tumor. Spontaneouspelvic cavity induction, retroperitoneal lymph node metastasis; Record the micetumor size and pelvic,retroperitoneal lymph node metastasis number (with HE dyeingaccurate), through the immunohistochemical method detection in situ tumor CD8+molecular expression，Use Tunel kit Test tumor cell apoptosis. Treatment model: willthe little black male C57BL/6rat (6to8weeks old) randomly divided into fourgroup: Taxol, Pub, Pub-MTDH, Pub-MTDH+Taxol (n=12), In each group micewere abdominal skin to vaccinate10~5RM-1cells, establish subcutaneous transplanttumor model, the mice after respectively in3,7,11days were given PBS, Pub,Pub-MTDH, Pub-MTDH DNA vaccine irrigation stomach servo immune three times,Taxol, Pub-MTDH+Taxol mice respectively in4,8,12days give paclitaxel (20mg/kg) with saline water dilute intraperitoneal injection of lookahead;Observesubcutaneous tumor growth situation, draw tumor growth curve, mice live tumor-burdened graph,27days off tumors are size and weight; Through the Tunelmethod to detect the tumor cell apoptosis, RT-PCR detection subcutaneous tumortissue Bcl-2, Bax gene expression.Results: MTDH/AEG-1-1gene in RM cell high expression, and in normal tissue inthe mice express very low. PUb-MTDH/AEG-1DNA vaccine compared to pUb, PBSwith the control group significantly stimulate CD4+and CD8+T cells and celltoxicity T lymphocytes (CTL) response; Inhibit the RM-1in situ prostate cancergrowth (p <0.001) and pelvic cavity, retroperitoneal lymph node metastasis (p <0.05); Obvious enhancement in situ tumor CD8+molecular expression (p <0.01),promote the tumor cell apoptosis(p <0.001). PUb-MTDH/AEG-1DNA vaccines withthe chemotherapy drug paclitaxel alone MTDH use with joint use/AEG-1, paclitaxel,pUb treatment group than can significantly inhibit the growth of prostate cancer（＊P<0.05）and prolong survival time tumor-burdened mice（＃P＜0.05）, promptingtumor tissue Bcl-2express cut, Bax over-active and promote the tumor cell apoptosis.Conclusions: To MTDH/AEG-1for the target gene vaccine can effectively restrainthe growth of prostate cancer in mice transfer and enhance the chemotherapy drugpaclitaxel sensitivity. MTDH/AEG-1DNA vaccines with the chemotherapy drugpaclitaxel in joint use the treatment of prostate cancer in show the advantages of good,we are looking forward to the gene vaccine can better with surgery, radiation therapycombined use, high expression in MTDH/AEG-1gene (prostate cancer, breast cancer,liver cancer, neuroblastoma, melanoma, esophageal, gastric cancer, etc) the treatmentof malignant tumor can play a big advantage.