Anti-MDR1 siRNA restores chemosensitivity in chemoresistant breast carcinoma and osteosarcoma cell lines.
Anticancer Res
; 31(9): 2813-20, 2011 Sep.
Article
em En
| MEDLINE
| ID: mdl-21868524
ABSTRACT
BACKGROUND:
Reversion of chemoresistance by inhibition of P-glycoprotein (P-gp) expression may overcome the chemoresistance observed in many cancer types and may allow for improved therapeutic ratio. We investigated whether siRNA specific for ABCB1 (MDR1) mRNA might restore sensitivity to chemotherapy in tumor cell lines known to overexpress the MDR1 gene. MATERIALS ANDMETHODS:
MDR1-expressing tumor cell lines were transiently transfected with anti-MDR1 silencing RNA (siRNA) before exposure to doxorubicin or methotrexate. The capacity of siRNA to reduce cell proliferation and increase the IC50 of the tested chemotherapies was investigated.RESULTS:
siRNA down-regulated MDR1 mRNA expression by 50% in breast carcinoma and osteosarcoma cell lines, and significantly inhibited tumor cell proliferation up to 90% (p<0.01), when co-administered with doxorubicin or methotrexate, despite the known chemoresistance of the cell lines. siRNAs reduced the IC50 of doxorubicin and methotrexate by more than 10-fold (p<0.01).CONCLUSION:
These results suggest the potential clinical application of anti-MDR1 siRNA to restore chemosensitivity and possibly improve the therapeutic ratio of these cytotoxic drugs.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Osteossarcoma
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Resistencia a Medicamentos Antineoplásicos
/
RNA Interferente Pequeno
Limite:
Female
/
Humans
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
França