title: β-elemene reverses chemoresistance of breast cancer via regulating MDR-related microRNA expression.
abstract: BACKGROUND
  Multidrug resistance (MDR) directly contributes to the clinical failure of chemotherapy in breast cancer (BCA). β-elemene is a natural antitumor drug from plants. We previously confirmed that MDR could be reversed by β-elemene. In this study, we intended to investigate the reversal effect of β-elemene on MDR in human BCA adriacin (Adr) -resistant MCF-7 cells (MCF-7/Adr) and docetaxel (Doc) - resistant MCF-7 cells (MCF-7/Doc) through the gene regulatory network.
  
  
  METHODS
  MTT-cytotoxic, miRNA microarray, Real-time quantitative PCR, Dual Luciferase Activity Assay, Western blot analysis were performed to investigate the impact of β-elemene on chemo-resistant BCA cell suvival, and its impact on the expression of chemo-resistance specific miRNA and the downstream target genes PTEN and Pgp.
  
  
  RESULTS
  Compared with the miRNAs expression profiles of MCF-7/Adr and MCF-7/Doc cell lines from our previous studies, there were 322 differentially expressed miRNAs in MCF-7/Adr and MCF-7/Doc breast cancer cells with β-elemene intervention (50μM/L) for 30h, and 6 miRNAs were significantly up-regulated and 12 miRNAs were significantly down-regulated in both MCF-7/Adr and MCF-7/Doc. We have testified that 5 miRNA is related to MDR before, in this study, the expression of miR-34a, miR-222, miR-452 and miR-29a can lead to changes of the characteristics of chemo-resistant MCF-7/Adr and MCF-7/Doc. The PTEN expression under intervention of β-elemene was significantly increased and Pgp expression under β-elemene intervention was significantly decreased in both cell lines.
  
  
  CONCLUSIONS
  β-elemene could influence MDR related miRNA expression and subsequently regulate the expression of the target genes PTEN and Pgp, which may lead to reduction of the viability of the chemo-resistant breast cancer cells.
authors.affiliation: Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: He da
authors.initials: Hd
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Da Wei
authors.initials: DW
authors.lastname: Sun
authors.forename: Chang fei
authors.initials: Cf
authors.lastname: Mao
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Jian Zhong
authors.initials: JZ
authors.lastname: Wu
authors.forename: Shan Liang
authors.initials: SL
authors.lastname: Zhong
authors.forename: Jian Hua
authors.initials: JH
authors.lastname: Zhao
authors.forename: Jin Hai
authors.initials: JH
authors.lastname: Tang
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000096:biosynthesis*; D012717:Sesquiterpenes / Q000008:administration & dosage*; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D000077143:Docetaxel; D004317:Doxorubicin; D035683:MicroRNAs; D012717:Sesquiterpenes; D043823:Taxoids; C525710:MIR222, human; C532045:MIRN29a microRNA, human; C522425:MIRN34 microRNA, human; C574051:MIRN452 microRNA, human; C038905:elemene