Delivery of the gene encoding the tumor suppressor Sef into prostate tumors by therapeutic-ultrasound inhibits both tumor angiogenesis and growth
Abstract Carcinomas constitute over 80% of all human cancer types with no effective therapy for metastatic disease. Here, we demonstrate, for the first time, the efficacy of therapeutic-ultrasound (TUS) to deliver a human tumor suppressor gene, hSef-b, to prostate tumors in vivo. Sef is downregulate...
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| Autores principales: | , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/18777b20c254425b9579b5a09b321728 |
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| Sumario: | Abstract Carcinomas constitute over 80% of all human cancer types with no effective therapy for metastatic disease. Here, we demonstrate, for the first time, the efficacy of therapeutic-ultrasound (TUS) to deliver a human tumor suppressor gene, hSef-b, to prostate tumors in vivo. Sef is downregulated in various human carcinomas, in a manner correlating with tumor aggressiveness. In vitro, hSef-b inhibited proliferation of TRAMP C2 cells and attenuated activation of ERK/MAPK and the master transcription factor NF-κB in response to FGF and IL-1/TNF, respectively. In vivo, transfection efficiency of a plasmid co-expressing hSef-b/eGFP into TRAMP C2 tumors was 14.7 ± 2.5% following a single TUS application. Repeated TUS treatments with hSef-b plasmid, significantly suppressed prostate tumor growth (60%) through inhibition of cell proliferation (60%), and reduction in blood vessel density (56%). In accordance, repeated TUS-treatments with hSef-b significantly inhibited in vivo expression of FGF2 and MMP-9. FGF2 is a known mitogen, and both FGF2/MMP-9 are proangiogenic factors. Taken together our results strongly suggest that hSef-b acts in a cell autonomous as well as non-cell autonomous manner. Moreover, the study demonstrates the efficacy of non-viral TUS-based hSef-b gene delivery approach for the treatment of prostate cancer tumors, and possibly other carcinomas where Sef is downregulated. |
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