Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells.
Mol Cancer Ther
; 5(5): 1342-51, 2006 May.
Article
em En
| MEDLINE
| ID: mdl-16731768
ABSTRACT
Genomic signaling mechanisms require a relatively long time to get into action and represent the main way through which steroid hormones affect target cells. In addition, steroids may rapidly activate cellular functions by non-genomic signaling mechanisms involving membrane sites. Understanding in depth the molecular mechanisms of the non-genomic action represents an important frontier for developing new and more selective pharmacologic tools for endocrine therapies. In the present study, we report that membrane-impermeable testosterone-bovine serum albumin (BSA) acts synergistically with paclitaxel in modifying actin and tubulin cytoskeleton dynamics in LNCaP (androgen sensitive) and DU-145 (androgen insensitive) human prostate cancer cell lines. In addition, coincubation of either cell line with testosterone-BSA and paclitaxel induced inhibition of cell proliferation and apoptosis. Finally, in vivo experiments in LNCaP and DU-145 tumor xenografts in nude mice showed that both agents decrease tumor mass, whereas testosterone-BSA enhances the effect of paclitaxel. Our findings suggest that chronic activation of membrane androgen receptors in vitro and in vivo facilitates and sustains for a longer time the antitumoral action of cytoskeletal acting agents.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Protocolos de Quimioterapia Combinada Antineoplásica
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Receptores Androgênicos
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Paclitaxel
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article