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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 RLS 40  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.

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