癌症研究
转移
前列腺癌
癌基因
CD8型
免疫系统
癌症
紫杉醇
细胞生长
生物
dna疫苗
血管生成
免疫学
医学
细胞周期
内科学
遗传学
免疫
作者
Chun Zhang,Huizhang Li,Benjiang Qian,Changming Liu,Fang Guo,Miao-Chun Lin
标识
DOI:10.1016/j.biopha.2015.01.028
摘要
MTDH/AEG-1 could act as an oncogene by regulating cellular transformation, proliferation, invasion, metastasis, and angiogenesis. This study aims to explore the mechanism by which MTDH/AEG-1 inhibits cancer growth and metastasis and enhances chemosensitivity. Mouse model was established using orally immunized mice exposed to attenuated Salmonella containing vectors carrying full length MTDH/AEG-1 gene, and we were able to enhance the immune response and inhibit the growth and metastasis of prostate cancer through activation of cellular and humoral immunities and induction of CD8+ T cells. Immunohistochemistry and TUNEL assay, CD4+ and CD8+ T cell analysis by flow cytometry, HE staining, RT-PCR analysis, Western-blot analysis and quantitative polymerase chain reaction were performed. The MTDH/AEG-1 gene vaccine induced the anti-tumor function of cytotoxic T lymphocytes and CD8+ T cells and inhibited tumor growth and metastasis of prostate cancer. In the therapy model, the MTDH/AEG-1 gene vaccine significantly enhanced chemosensitivity to paclitaxel, inhibited tumor growth, promoted tumor cell apoptosis, and prolonged the survival time of tumor-bearing mice without any apparent side effects. Our results demonstrated that MTDH/AEG-1-based DNA vaccines could used for the treatment of prostate cancer in terms of the inhibition of tumor growth, the lifespan of tumor-bearing animals. Combined with chemotherapy, MTDH/AEG-1-based DNA vaccines may produce highly favorable outcomes in the prevention and treatment of prostate cancer, suggesting the immune efficacy of MTDH/AEG-1-based DNA should be further analyzed in other cancers.
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