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Open Access Research article

The siRNA targeted to mdr1b and mdr1a mRNAs in vivo sensitizes murine lymphosarcoma to chemotherapy

Olga A Patutina1, Nadezda L Mironova1, Nelly A Popova2, Vasily I Kaledin2, Valery P Nikolin2, Valentin V Vlassov1 and Marina A Zenkova1*

Author Affiliations

1 Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Lavrentiev av. 8, Novosibirsk, 630090 Russia

2 Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Lavrentiev av. 10, Novosibirsk, 630090 Russia

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BMC Cancer 2010, 10:204  doi:10.1186/1471-2407-10-204

Published: 14 May 2010

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.