title: Matrine inhibits breast cancer growth via miR-21/PTEN/Akt pathway in MCF-7 cells.
abstract: BACKGROUND
  Matrine is one of the major alkaloids extracted from Sophora flavescens and has been used clinically for breast cancer with notable therapeutic efficacy in China. However, the mechanisms are still largely unknown.
  
  
  METHODS
  Cell viability was analyzed by MTT assay. After MCF-7 cells were treated with matrine for 48h, apoptosis was detected by flow cytometry, TUNEL assay and transmission electron microscopy, and the cell cycle distribution was also analyzed by flow cytometry. Further, the expression of PTEN, pAkt, Akt, pBad, Bad, p21(/WAF1/CIP1), and p27(/KIP1) was determined by Western blot. Changes of miR-21 level were quantified by real-time RT-PCR. After miR-21 was transfected in MCF-7 cells, PTEN protein level was measured by Western blot.
  
  
  RESULTS
  Matrine inhibited MCF-7 cell growth in a concentration-and time-dependent manner, by inducing apoptosis and cell cycle arrest at G(1)/S phase. Matrine up-regulated PTEN by downregulating miR-21 which in turn dephosphorylated Akt, resulting in accumulation of Bad, p21(/WAF1/CIP1) and p27(/KIP1).
  
  
  CONCLUSIONS
  Our study unraveled, for the first time, the ability of matrine to suppress breast cancer growth and elucidated the miR-21/PTEN/Akt pathway as a signaling mechanism for the anti-cancer action of matrine. Our findings also reinforce the notion that miRNAs can act as mediators of the therapeutic efficacy of natural medicines.
authors: Key Laboratory of Hepatosplenic Surgery, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Lin-Qiang
authors: LQ
authors: Li
authors: Xue-Lian
authors: XL
authors: Li
authors: Lu
authors: L
authors: Wang
authors: Wei-Jie
authors: WJ
authors: Du
authors: Rui
authors: R
authors: Guo
authors: Hai-Hai
authors: HH
authors: Liang
authors: Xue
authors: X
authors: Liu
authors: De-Sen
authors: DS
authors: Liang
authors: Yan-Jie
authors: YJ
authors: Lu
authors: Hong-Li
authors: HL
authors: Shan
authors: Hong-Chi
authors: HC
authors: Jiang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011807:Quinolizines / Q000494:pharmacology*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D050759:Cyclin-Dependent Kinase Inhibitor p21; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D011807:Quinolizines; D051025:bcl-Associated Death Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D000093842:Matrines