MTDH/AEG-1-based DNA vaccine suppresses metastasis and enhances chemosensitivity to paclitaxel in pelvic lymph node metastasis
| Autor: | Huizhang Li, Chun Zhang, Fang Guo, Changming Liu, Miao-Chun Lin, Ben-Jiang Qian |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Paclitaxel Angiogenesis T cell Administration Oral Metastasis Mice Prostate cancer Cell Line Tumor Vaccines DNA medicine Animals Cytotoxic T cell Pelvic Neoplasms Pharmacology Oncogene business.industry Membrane Proteins Prostatic Neoplasms RNA-Binding Proteins Cancer MTDH General Medicine medicine.disease Antineoplastic Agents Phytogenic Mice Inbred C57BL Survival Rate medicine.anatomical_structure Drug Resistance Neoplasm Lymphatic Metastasis Cancer research business |
| Zdroj: | Biomedicine & Pharmacotherapy. 70:217-226 |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2015.01.028 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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