Chun Zhang1, Hui-Zhang Li2, Ben-Jiang Qian1, Chang-Ming Liu1, Fang Guo3, Miao-Chun Lin1. 1. Institute of Ningde Urological Research and Department of Urology, Affiliated Mindong Hospital of Fujian Medical University, No. 89, Heshan Road, Fu'an, Fujian 355000, China. 2. Institute of Ningde Urological Research and Department of Urology, Affiliated Mindong Hospital of Fujian Medical University, No. 89, Heshan Road, Fu'an, Fujian 355000, China. Electronic address: huizhang_li@126.com. 3. Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences-Shanghai Jiao-Tong University School of Medicine (SJTU-SM), No. 225, South Chongqing Road, Shanghai 200025, China.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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.