title: The siRNA targeted to mdr1b and mdr1a mRNAs in vivo sensitizes murine lymphosarcoma to chemotherapy.
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.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Lavrentiev av, 8, Novosibirsk, 630090 Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Patutina
authors.forename: Nadezda L
authors.initials: NL
authors.lastname: Mironova
authors.forename: Nelly A
authors.initials: NA
authors.lastname: Popova
authors.forename: Vasily I
authors.initials: VI
authors.lastname: Kaledin
authors.forename: Valery P
authors.initials: VP
authors.lastname: Nikolin
authors.forename: Valentin V
authors.initials: VV
authors.lastname: Vlassov
authors.forename: Marina A
authors.initials: MA
authors.lastname: Zenkova
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D005838:Genotype; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010641:Phenotype; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C095122:multidrug resistance protein 3
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