Paclitaxel and TRAIL synergize to kill paclitaxel-resistant small cell lung cancer cells through a caspase-independent mechanism mediated through AIF.
Anticancer Res
; 31(10): 3193-204, 2011 Oct.
Article
en En
| MEDLINE
| ID: mdl-21965726
ABSTRACT
BACKGROUND:
Small cell lung cancer (SCLC) is the most aggressive form of lung cancer with poor disease outcome. The chemotherapeutic agent paclitaxel (PA) is commonly used as a second-line treatment in SCLC, but response rates are low. MATERIALS ANDMETHODS:
86M1 SCLC cells were treated in the presence or absence of paclitaxel and TRAIL or the combination for 24 hours. Western blot analysis was utilized to examine protein expression, cell surface protein expression and membrane integrity were elucidated by flow cytometry, and immunofluorescence microscopy was used to demonstrate translocation of proteins to the cell nucleus.RESULTS:
Human 86M1 SCLC cells were found to be resistant to PA killing in vitro. This resistance is mediated by up-regulation of pro-survival protein BCL-xl. However, PA also increases surface expression of death receptors 4 and 5 (DR4 and DR5, respectively). The death receptors' ligand increased SCLC killing by PA through an apparent caspase-independent route involving activation/translocation of AIF.CONCLUSION:
The addition of TRAIL to PA can potentiate apoptosis in a relatively PA-resistant SCLC line (specifically 86M1 cells). More importantly, we are the first to report an active method of resistance to paclitaxel in SCLC via BCL-xl up-regulation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Paclitaxel
/
Apoptosis
/
Resistencia a Antineoplásicos
/
Factor Inductor de la Apoptosis
/
Ligando Inductor de Apoptosis Relacionado con TNF
/
Carcinoma Pulmonar de Células Pequeñas
/
Neoplasias Pulmonares
Límite:
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos