title: Astragaloside II sensitizes human hepatocellular carcinoma cells to 5-fluorouracil via suppression of autophagy.
abstract: OBJECTIVE
  Inhibition of autophagy has been increasingly recognized as a potential therapeutic approach against cancer. Our previous reports showed that Astragaloside II improves hepatic cancer cells resistance by downregulating MDR1 and P-gp .The purpose of this study was to further investigated the effect of autophagy on AS-II reversing multidrug resistance and its molecular mechanism in hepatocellular carcinoma cells in vitro.
  
  
  METHODS
  Bel-7402 and Bel-7402/FU cell lines were used in this study. Western blot was used to detect the expression of autophagy-related protein, p-mTOR and p-p79s6k, MTT was used to analyse cell viability, GFP-LC3 punctate dots distribution was observed by GFP-LC3 transient transfection under fluorescence microscopy and silencing of autophagy-related genes was detected by small interfering RNA transfection.
  
  
  RESULTS
  Astragaloside II was able to significantly decrease the expression of LC3-II and Beclin-1 in a dose-dependent manner, Astragaloside II (80 μm) further decreased LC3-II formation, Beclin-1 and GFP-LC3 puncta dots stimulated with 5-fluorouracil (0.2 mm) in Bel-7402/FU cells (P < 0.05). In addition, Astragaloside II is capable of sensitizing cells to 5-fluorouracil-induced cell death via inhibition of pro-survival autophagy involvement of MAPK-mTOR pathway.
  
  
  CONCLUSIONS
  These findings suggested that Astragaloside II could suppress autophagy by interfering with Beclin-1 and LC3 via MAPK-mTOR pathway, through which sensitized human cancer resistant cells to 5-FU-induced cell death.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Affiliated Anqing Hospital of Anhui Medical University, Anqing, Anhui, China.
authors.forename: Can
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Pharmacy, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Du-Juan
authors.initials: DJ
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D034622:RNA Interference / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D034741:RNA, Small Interfering; D012503:Saponins; C580601:astragaloside II; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D005472:Fluorouracil
keywords: Astragaloside II; MAPK-mTOR; autophagy; sensitization