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

• Published in: BMC cancer 2010-05, Vol.10 (1), p.204-204
• Main Authors: Patutina, Olga A, Mironova, Nadezda L, Popova, Nelly A, Kaledin, Vasily I, Nikolin, Valery P, Vlassov, Valentin V, Zenkova, Marina A
• Format: Article
• Language: English
• Subjects: ABC transporters; Animals; Antineoplastic Agents, Alkylating - pharmacology; Apoptosis; ATP Binding Cassette Transporter, Subfamily B - genetics; ATP-Binding Cassette Sub-Family B Member 4; Breeding of animals; Cancer; Cancer therapies; Chemotherapy; Clinical medicine; Complications and side effects; Cyclophosphamide - pharmacology; Drug resistance; Drug Resistance, Neoplasm - genetics; Drug therapy; Experiments; Gene Expression Regulation, Neoplastic; Genetic aspects; Genetic Therapy - methods; Genotype; Genotype & phenotype; Hodgkin's disease; Laboratory animals; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - genetics; Lymphoma, Non-Hodgkin - metabolism; Lymphoma, Non-Hodgkin - pathology; Lymphoma, Non-Hodgkin - therapy; Male; Mice; Mice, Inbred CBA; Mortality; Phenotype; RNA Interference; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; Time Factors; Transfection; Tumor Burden; Tumor Cells, Cultured; Tumors
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-10-204

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.). 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. 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. In perspective, mdr1b/1a siRNA may become a well-reasoned adjuvant tool in the therapy of MDR malignancies.