The siRNA targeted to mdr1b and mdr1a mRNAs in vivo sensitizes murine lymphosarcoma to chemotherapy.
BMC Cancer
; 10: 204, 2010 May 14.
Article
em En
| MEDLINE
| ID: mdl-20470373
ABSTRACT
BACKGROUND:
One of the main obstacles for successful cancer polychemotherapy is multiple drug resistance phenotype (MDR) acquired by tumor cells. Currently, RNA interference represents a perspective strategy to overcome MDR via silencing the genes involved in development of this deleterious phenotype (genes of ABC transporters, antiapoptotic genes, etc.).METHODS:
In this study, we used the siRNAs targeted to mdr1b, mdr1a, and bcl-2 mRNAs to reverse the MDR of tumors and increase tumor sensitivity to chemotherapeutics. The therapy consisting in ex vivo or in vivo application of mdr1b/1a siRNA followed by cyclophosphamide administration was studied in the mice bearing RLS40 lymphosarcoma, displaying high resistance to a wide range of cytostatics.RESULTS:
Our data show that a single application of mdr1b/1a siRNA followed by treatment with conventionally used cytostatics results in more than threefold decrease in tumor size as compared with the control animals receiving only cytostatics.CONCLUSIONS:
In perspective, mdr1b/1a siRNA may become a well-reasoned adjuvant tool in the therapy of MDR malignancies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfoma não Hodgkin
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Terapia Genética
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Resistencia a Medicamentos Antineoplásicos
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Antineoplásicos Alquilantes
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Subfamília B de Transportador de Cassetes de Ligação de ATP
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Ciclofosfamida
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RNA Interferente Pequeno
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Interferência de RNA
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article