title: Downregulation of gene MDR1 by shRNA to reverse multidrug-resistance of ovarian cancer A2780 cells.
abstract: BACKGROUND
  To explore the effects of downregulated multidrug-resistance P-glycoprotein (MDR1/ABCB1) and reversed multidrug-resistance in human A2780 ovarian cancer cells.
  
  
  METHODS
  Three shRNAs targeting the MDR1 gene were synthesized, and cloned into plasmid pSUPER-enhanced green fluorescent protein 1 (EGFP1). The formed pSUPER-EGFP1-MDR1-shRNAs were transfected into the A2780 cells, respectively, and the quantitative reverse transcription polymerase chain reaction and western blot were used respectively to determine the MDR1 expression. The multidrug-resistance (MDR) of the MDR1-shRNAs transfected A2780 cells to chemotherapy drugs in vitro and in tumor-bearing nude mice were respectively evaluated.
  
  
  RESULTS
  The MDR1 shRNA expression resulted in decreased P-glycoprotein expression in the transfected A2780 cells. The MDR1-shRNA2 transfected cells showed that the sensitivities to chemotherapy drugs were higher than other shRNAs transfected A2780 cells, and that the formed tumor in mice grew slower than those of other mice after paclitaxel was injected into tumor-bearing nude mice.
  
  
  CONCLUSIONS
  Our data demonstrates that the RNA interference could knock down gene MDR1 and reduce the P-glycoprotein expression, and partly reverse the MDR of A2780 cells in vitro and in vivo. These results suggest that MDR-1 is an effective therapeutic target for human ovarian caner treatment.
authors: Department of Pathogenic Biology and Immunology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.
authors: Hongyi
authors: H
authors: Zhang
authors: Jing
authors: J
authors: Wang
authors: Kai
authors: K
authors: Cai
authors: Longwei
authors: L
authors: Jiang
authors: Dandan
authors: D
authors: Zhou
authors: Cuiping
authors: C
authors: Yang
authors: Junsong
authors: J
authors: Chen
authors: Dengyu
authors: D
authors: Chen
authors: Jun
authors: J
authors: Dou
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D000077143:Docetaxel; D015536:Down-Regulation; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D043823:Taxoids / Q000494:pharmacology; D047368:Tumor Burden; D014750:Vincristine / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D043823:Taxoids; D000077143:Docetaxel; D014750:Vincristine; D017239:Paclitaxel; D002945:Cisplatin