title: Combination of Matrine and Sorafenib Decreases the Aggressive Phenotypes of Hepatocellular Carcinoma Cells.
abstract: BACKGROUND
  The aim of this study was to determine the effects of matrine (a natural alkaloid) on sorafenib-induced cytotoxicity against hepatocellular carcinoma (HCC) cells, and to explore the molecular mechanisms involved.
  
  
  METHODS
  HepG2 and Hep3B cells were treated with matrine alone or in combination with sorafenib, and cell viability and apoptosis were assessed. The involvement of micro (mi)RNA-21 in the action of matrine was examined.
  
  
  RESULTS
  Matrine significantly augmented the antiproliferative activity of sorafenib in a dose-dependent manner. Matrine significantly increased apoptosis, coupled with enhanced cleavage of caspase-3 and poly (ADP-ribose) polymerase. miRNA-21-overexpressing HCC cells showed a marked decrease in matrine-induced growth suppression and the expression of phosphatase and tensin homolog (PTEN). The suppressive effect of combining matrine and sorafenib was significantly reduced by miRNA-21 overexpression or PTEN inhibition.
  
  
  CONCLUSIONS
  Matrine in combination with sorafenib leads to increased cytotoxic effects against HCC cells, at least partially, via the suppression of miRNA-21 and the subsequent induction of PTEN.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Lianjie
authors.initials: L
authors.lastname: Lin
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dongxu
authors.initials: D
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Tan
authors.forename: Changqing
authors.initials: C
authors.lastname: Zheng
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010641:Phenotype; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011807:Quinolizines / Q000008:administration & dosage; D000077157:Sorafenib; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011807:Quinolizines; D009536:Niacinamide; D000077157:Sorafenib; D000093842:Matrines