title: Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1.
abstract: BACKGROUND
  Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. Erythroblastosis virus E26 oncogene homolog 1 (ETS1) is involved in the drug resistance of various cancer cells, and is overexpressed in drug-resistant human breast cancer cell lines. In this study, we investigated the effects of ETS1 on adriamycin resistance in MCF-7/ADR cells.
  
  
  METHODS
  siRNAs against ETS1 or negative control siRNAs was transfected to MCF-7/ADR breast cancer cells. Reverse transcription-PCR and Western blotting were used to determine the mRNA and protein expression of ETS1 and MDR1. The cytotoxicity of adriamycin was assessed using the MTT assay. Drug efflux was investigated by flow cytometry using the Rhodamine 123 intracellular accumulation assay.
  
  
  RESULTS
  ETS1 mRNA and protein was significantly overexpressed in MCF-7/ADR cells, compared to MCF-7 cells. ETS1 siRNA successfully silenced ETS1 mRNA and protein expression. Silencing of ETS1 also significantly reduced the mRNA and protein expression levels of MDR1 (multidrug resistance 1; also known as ABCB1, P-glycoprotein/P-gp), which is a major ATP-binding cassette (ABC) transporter linked to multi-drug resistance in cancer cells. Silencing of ETS1 significantly increased the sensitivity of MCF-7/ADR cells to adriamycin, compared to cells transfected with negative control siRNA. In addition, intracellular accumulation of Rhodamine 123 significantly increased in MCF-7/ADR cells transfected with ETS1 siRNA, indicating that silencing of ETS1 may reduce drug efflux.
  
  
  CONCLUSIONS
  This study demonstrates that drug resistance can be effectively reversed in adriamycin-resistant breast carcinoma cells through delivery of siRNAs targeting ETS1.
authors.affiliation: Department of General Surgery, The Second Affiliated of Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of General Surgery, Yancheng City No. 1 People's Hospital, Yancheng, Jiangsu 224005, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, The Second Affiliated of Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Guo-Qin
authors.initials: GQ
authors.lastname: Jiang
authors.affiliation: Department Urology, University of Pittsburgh Cancer Institute, University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Suit G37, 5200 Center Avenue, Pittsburgh, PA 15232, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao