Adenoviral-mediated gene therapy of human bladder cancer with antisense interleukin-8.
Oncol Rep
; 8(5): 955-64, 2001.
Article
en En
| MEDLINE
| ID: mdl-11496299
ABSTRACT
We previously demonstrated the importance of interleukin-8 (IL-8) as a mediator of angiogenesis, tumorigenicity, and metastasis of transitional cell carcinoma (TCC) of the bladder. In the present study, we evaluated the feasibility of adenoviral mediated antisense IL-8 gene transfer (Ad IL-8-AS) as therapy for established TCC. In vitro, Ad IL-8-AS inhibited endothelial cell proliferation and enhanced endothelial cell apoptosis. The highly metastatic human TCC cell line 253J B-V(R) was implanted into the subcutis of athymic nude mice, and intralesional therapy with Ad IL-8-AS commenced when the tumors reached a diameter between 5 and 7 mm. Tumor growth was significantly inhibited compared with therapy in controls (saline and beta-galactosidase adenovirus). Ad IL-8-AS therapy decreased the in vivo expression of IL-8 and matrix metalloproteinase type 9 (MMP-9), reduced microvessel density, and enhanced endothelial cell apoptosis. These results indicate that Ad IL-8-AS therapy targets both tumor cells and host endothelial cells resulting in endothelial cell apoptosis and significant inhibition of tumor growth.
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Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Vejiga Urinaria
/
Carcinoma de Células Transicionales
/
Terapia Genética
/
Adenoviridae
/
Elementos sin Sentido (Genética)
/
Interleucina-8
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos