Title |
Anti-tumor effects of a recombinant anti-prostate specific membrane antigen immunotoxin against prostate cancer cells
|
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Published in |
BMC Urology, February 2017
|
DOI | 10.1186/s12894-017-0203-9 |
Pubmed ID | |
Authors |
Ping Meng, Qing-chuan Dong, Guang-guo Tan, Wei-hong Wen, He Wang, Geng Zhang, Yan-zhu Wang, Yu-ming Jing, Chen Wang, Wei-jun Qin, Jian-lin Yuan |
Abstract |
To evaluate anti-prostate cancer effects of a chimeric tumor-targeted killer protein. We established a novel fusion gene, immunocasp-3, composed of NH2-terminal leader sequence fused with an anti-prostate-specific membrane antigen (PSMA) antibody (J591), the furin cleavage sequences of diphtheria toxin (Fdt), and the reverse coding sequences of the large and small subunits of caspase-3 (revcaspase-3). The expressing level of the immunocasp-3 gene was evaluated by using the reverse transcription-PCR (RT-PCR) and western blot analysis. Cell viability assay and cytotoxicity assay were used to evaluate its anti-tumor effects in vitro. Apoptosis was confirmed by electron microscopy and Annexin V-FITC staining. The antitumor effects of immunocasp-3 were assessed in nude mice xenograft models containing PSMA-overexpressing LNCaP cells. This study shows that the immunocasp-3 proteins selectively recognized and induced apoptotic death in PSMA-overexpressing LNCaP cells in vitro, where apoptotic cells were present in 15.3% of the cells transfected with the immunocasp-3 expression vector at 48 h after the transfection, in contrast to 5.5% in the control cells. Moreover, LNCaP cells were significantly killed under the condition of the co-culture of the immunocasp-3-secreting Jurkat cells and more than 50% of the LNCaP cells died when the two cell lines were co-cultured within 5 days. In addition, The expression of immunocasp-3 also significantly suppressed tumor growth and greatly prolonged the animal survival rate in vivo. A novel fusion gene, immunocasp-3, may represent a viable approach to treating PSMA-positive prostate cancer. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 25 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 6 | 24% |
Student > Bachelor | 3 | 12% |
Student > Doctoral Student | 2 | 8% |
Student > Postgraduate | 2 | 8% |
Student > Ph. D. Student | 2 | 8% |
Other | 4 | 16% |
Unknown | 6 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 3 | 12% |
Medicine and Dentistry | 3 | 12% |
Agricultural and Biological Sciences | 2 | 8% |
Chemistry | 2 | 8% |
Immunology and Microbiology | 2 | 8% |
Other | 5 | 20% |
Unknown | 8 | 32% |