Suppression of STAT3 by chemically modified siRNAs increases the chemotherapeutic sensitivity of parental and cisplatin-resistant non-small cell lung cancer cells.
J BUON
; 19(1): 145-52, 2014.
Article
em En
| MEDLINE
| ID: mdl-24659656
ABSTRACT
PURPOSE:
Increased activation of the JAK-STAT signaling pathway is frequently observed in several primary cancers as well as cancer cell lines. Thus, targeting JAK-STAT pathway components by different molecular-biologic approaches in the search for new anticancer therapies has become widespread and resulted in encouraging outcomes. In this study, the effects of chemically modified anti-STAT3 small interfering (si)RNAs on cell viability, proliferation and apoptosis of parental and cisplatin resistant non-small cell lung cancer (NSCLC) cells were investigated with the aim to provide a new therapeutic strategy for overcoming cisplatin resistance in lung cancer.METHODS:
The parental NSCLC cell line Calu1 and its cisplatin- resistant subline CR-Calu1 were used to study the effects of STAT3 suppression with chemically modified anti-STAT3 siRNAs. STAT3 gene and protein expressions were analyzed by real-time (RT) quantitative (q) PCR and Western blot, respectively. Apoptosis was evaluated by Caspase-3 activity and cell death assays.RESULTS:
STAT3 messenger (m)RNA and protein expression were significantly increased in CR-Calu1 cells and suppressing its expression with specific siRNAs increased the rate of apoptosis through Caspase-3 activation. STAT3 suppression also significantly increased cisplatin sensitivity of Calu1 and CR-Calu1 cells after transfection with STAT3 siRNAs.CONCLUSIONS:
NSCLC cells could be sensitized to cisplatin by targeting STAT3 with chemically modified siRNAs together, a fact which was accompanied with increased apoptosis.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Resistencia a Medicamentos Antineoplásicos
/
RNA Interferente Pequeno
/
Fator de Transcrição STAT3
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
J BUON
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Turquia