Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma.
Cancer Sci
; 97(12): 1388-95, 2006 Dec.
Article
em En
| MEDLINE
| ID: mdl-17032313
ABSTRACT
The endothelin A receptor (ET(A)R) autocrine pathway is overexpressed in many malignancies, including nasopharyngeal carcinoma (NPC). In this tumor, ET(A)R expression is an independent determinant of survival and a robust independent predictor of distant metastasis. To evaluate whether ET(A)R represents a new target in NPC treatment, we tested the therapeutic role of ET(A)R in NPC. Cell proliferation was inhibited by the ET(A)R-selective antagonist ABT-627 in two ET(A)R-positive NPC cells in a dose-dependent manner. Proliferation of ET(A)R-negative NPC cells was not decreased. ET(A)R blockade also resulted in sensitization to cisplatin and 5-fluorouracil-induced apoptosis. In nude mice, ABT-627 inhibited the growth of NPC cell xenografts. Combined treatment of ABT-627 with the cytotoxic drug cisplatin or 5-fluorouracil produced additive antitumor effects. The antitumor activity of ABT-627 was demonstrated finally on an experimental lung metastasis by a reduction in the number of tumors. These results support the rationale of combining ABT-627 with current standard chemotherapy to further improve the therapeutic ratio in the treatment of NPC.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Nasofaríngeas
/
Antagonistas do Receptor de Endotelina A
/
Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article