Paclitaxel treatment of breast cancer cell lines modulates Fas/Fas ligand expression and induces apoptosis which can be inhibited through the CD40 receptor.
Oncology
; 66(2): 101-11, 2004.
Article
en En
| MEDLINE
| ID: mdl-15138361
ABSTRACT
OBJECTIVE:
Cytotoxic chemotherapy of advanced breast cancer is frequently complicated by drug resistance. Our goal was to define the role of the apoptosis-regulating receptors Fas (CD95) and CD40 in the chemosensitivity of breast cancer.METHODS:
The sensitivity of four breast cancer cell lines to paclitaxel and mitoxantrone was evaluated using an ATP-based cell viability assay. After verification of apoptosis by annexin V staining and TUNEL assay, cell lines were characterized regarding their constitutive expression of both surface and soluble (s)Fas (CD95) and Fas ligand (Fas-L). The role of the Fas/Fas-L system and different caspases was assessed by blocking drug-mediated apoptosis with specific antibodies. Finally, the paclitaxel sensitivity of the CD40-negative cell line KS was compared to that of its CD40-positive transfectant KS-CD40. RESULTS ANDCONCLUSION:
While the cytotoxic effect of mitoxantrone did not correlate with Fas expression, the results presented here suggest some involvement of the Fas/Fas-L system in paclitaxel-induced apoptosis. Cell lines with constitutive expression of Fas/sFas demonstrated a higher sensitivity to paclitaxel than Fas-negative cells. Incubation with paclitaxel led to a measurable downregulation of the expression of both soluble and surface Fas receptor in these cells. Interestingly, stimulation of the CD40 receptor inhibited paclitaxel-induced apoptosis in the transfected cell line KS-CD40, suggesting a role of this receptor in the modulation of chemosensitivity.
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Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Glicoproteínas de Membrana
/
Paclitaxel
/
Apoptosis
/
Receptor fas
/
Ligando de CD40
/
Antineoplásicos Fitogénicos
Límite:
Female
/
Humans
Idioma:
En
Año:
2004
Tipo del documento:
Article