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- Title
Anti-tumor effects of a recombinant anti-prostate specific membrane antigen immunotoxin against prostate cancer cells.
- 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; Meng, Ping; Dong, Qing-Chuan; Tan, Guang-Guo; Wen, Wei-Hong; Wang, He; Zhang, Geng; Wang, Yan-Zhu; Jing, Yu-Ming; Wang, Chen
- Abstract
<bold>Background: </bold>To evaluate anti-prostate cancer effects of a chimeric tumor-targeted killer protein.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>A novel fusion gene, immunocasp-3, may represent a viable approach to treating PSMA-positive prostate cancer.
- Subjects
TUMOR prevention; PROSTATE-specific membrane antigen; ANTIBODY-toxin conjugates; PROSTATE cancer treatment; CANCER cells; REVERSE transcriptase polymerase chain reaction; WESTERN immunoblotting; CANCER treatment; PROSTATE tumors treatment; ADENOCARCINOMA; ANIMALS; ANTIGENS; GENE therapy; GENETIC techniques; MICE; PROSTATE tumors; PROTEINS; PROTEOLYTIC enzymes; TOXINS; CANCER cell culture
- Publication
BMC Urology, 2017, Vol 17, p1
- ISSN
1471-2490
- Publication type
journal article
- DOI
10.1186/s12894-017-0203-9