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Anti-tumor effects of a recombinant anti-prostate specific membrane antigen immunotoxin against prostate cancer cells.
Meng, Ping; Dong, Qing-Chuan; Tan, Guang-Guo; Wen, Wei-Hong; Wang, He; Zhang, Geng; Wang, Yan-Zhu; Jing, Yu-Ming; Wang, Chen; Qin, Wei-Jun; Yuan, Jian-Lin.
Afiliação
  • Meng P; Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • Dong QC; Department of Urology Surgery, Peoples' Hospital of Shaanxi Province, Xi'an, Shaanxi, China.
  • Tan GG; Department of Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • Wen WH; Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • Wang H; Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
  • Zhang G; Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • Wang YZ; Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • Jing YM; Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • Wang C; State Key Laboratory of NBC Protection for Civilian, Beijing, China.
  • Qin WJ; Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. weijunqfmmu@163.com.
  • Yuan JL; Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. jianliny@fmmu.edu.cn.
BMC Urol ; 17(1): 14, 2017 Feb 13.
Article em En | MEDLINE | ID: mdl-28193277
BACKGROUND: To evaluate anti-prostate cancer effects of a chimeric tumor-targeted killer protein. METHODS: 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. RESULTS: 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. CONCLUSION: A novel fusion gene, immunocasp-3, may represent a viable approach to treating PSMA-positive prostate cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Terapia Genética / Adenocarcinoma / Glutamato Carboxipeptidase II / Antígenos de Superfície Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Terapia Genética / Adenocarcinoma / Glutamato Carboxipeptidase II / Antígenos de Superfície Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article