title: Triptolide modulates the sensitivity of K562/A02 cells to adriamycin by regulating miR-21 expression.
abstract: BACKGROUND
  Multidrug-resistance is a serious obstacle encountered in leukemia treatment. Recent studies have shown microRNA-21 (miR-21) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. In our previous studies, we found triptolide (TPL) could enhance adriamycin-induced cytotoxicity and apoptosis in K562/A02 cells.
  
  
  OBJECTIVE
  In the present study, we investigated the mechanism of TPL on the sensitivity of K562/A02 cells to adriamycin.
  
  
  METHODS
  Cell viability was assessed by methyl thiazolyl tetrazolium (MTT) assay. Expression of mature miR-21 was determined by SYBER green PCR. The miR-21 mimics and inhibitors were chemically synthesized and transfected into K562 cells or K562/A02 cells. PTEN protein levels was determined by western blots. PTEN promoter activity was measured by luciferase assays.
  
  
  RESULTS
  TPL (5 nmol/L) increased the sensitivity of K562/A02 to adriamycin. When adriamycin was combined with 5 nmol/L TPL, the mean apoptotic population of K562/A02 cells was increased from 4.3 to 18.5%, respectively. K562/A02 cells showed a significant reduction in miR-21 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) expressions after TPL treatment. K562/A02 cells that were transfected with the miR-21 inhibitor had a significantly higher PTEN protein level than the control. K562 cells that were pre-treated with PTEN siRNA had increased survival rate compared to the control group.
  
  
  CONCLUSIONS
  Our findings indicated that triptolide modulates the sensitivity of K562/A02 cells to adriamycin by regulating miR-21 expression. Triptolide inhibited miR-21 expression and enhanced PTEN levels in K562/A02 cells.
authors.affiliation: Department of Central Laboratory,The Affiliated People’s Hospital, Jiangsu University, Jiangsu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Lulu
authors.initials: L
authors.lastname: Hui
authors.forename: Wenlin
authors.initials: W
authors.lastname: Xu
authors.forename: Huiling
authors.initials: H
authors.lastname: Shen
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Chen
authors.forename: Lulu
authors.initials: L
authors.lastname: Long
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010616:Phenanthrenes / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
chemical_list: D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D010616:Phenanthrenes; C001899:triptolide; D004317:Doxorubicin; D051059:PTEN Phosphohydrolase