The siRNA targeted to <it>mdr1b </it>and <it>mdr1a </it>mRNAs <it>in vivo </it>sensitizes murine lymphosarcoma to chemotherapy

• Main Authors: Vlassov Valentin V, Nikolin Valery P, Kaledin Vasily I, Popova Nelly A, Mironova Nadezda L, Patutina Olga A, Zenkova Marina A
• Format: Article
• Language: English
• Published: BMC 2010-05-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/10/204

<p>Abstract</p> <p>Background</p> <p>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.).</p> <p>Methods</p> <p>In this study, we used the siRNAs targeted to <it>mdr1b, mdr1a</it>, and <it>bcl-2 </it>mRNAs to reverse the MDR of tumors and increase tumor sensitivity to chemotherapeutics. The therapy consisting in <it>ex vivo </it>or <it>in vivo </it>application of mdr1b/1a siRNA followed by cyclophosphamide administration was studied in the mice bearing RLS₄₀lymphosarcoma, displaying high resistance to a wide range of cytostatics.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>In perspective, mdr1b/1a siRNA may become a well-reasoned adjuvant tool in the therapy of MDR malignancies.</p>