title: Gambogic acid-loaded magnetic Fe(3)O(4) nanoparticles inhibit Panc-1 pancreatic cancer cell proliferation and migration by inactivating transcription factor ETS1.
abstract: BACKGROUND
  E26 transformation-specific sequence-1 (ETS1) transcription factor plays important roles in both carcinogenesis and the progression of a wide range of malignancies. Aberrant ETS1 expression correlates with aggressive tumor behavior and a poorer prognosis in patients with various malignancies. The aim of the current study was to evaluate the efficacy of a drug delivery system utilizing gambogic acid-loaded magnetic Fe(3)O(4) nanoparticles (GA-MNP-Fe(3)O(4)) on the suppression of ETS1-mediated cell proliferation and migration in Panc-1 pancreatic cancer cells.
  
  
  METHODS
  The effects caused by GA-MNP-Fe(3)O(4) on the proliferation of Panc-1 pancreatic cancer cells were evaluated using a MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay while inhibition of tumor cell migration was investigated in a scratch assay. The expressions of ETS1, cyclin D1, urokinase-type plasminogen activator (u-PA), and VEGF (vascular endothelial growth factor) were examined by Western blot to elucidate the possible mechanisms involved.
  
  
  RESULTS
  In Panc-1 pancreatic cancer cells, we observed that application of GA-MNP-Fe(3)O(4) was able to suppress cancer cell proliferation and prevent cells from migrating effectively. After treatment, Panc-1 pancreatic cancer cells showed significantly decreased expression of ETS1, as well as its downstream target genes for cyclin D1, u-PA, and VEGF.
  
  
  CONCLUSIONS
  Our novel finding reaffirmed the significance of ETS1 in the treatment of pancreatic cancer, and application of GA-MNP-Fe(3)O(4) nanoparticles targeting ETS1 should be considered as a promising contribution for better pancreatic cancer care.
authors.affiliation: Department of Oncology, Zhongda Hospital, Nanjing, People's Republic of China.
authors.forename: Cailian
authors.initials: C
authors.lastname: Wang
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Fangfang
authors.initials: F
authors.lastname: Shi
authors.forename: Baoan
authors.initials: B
authors.lastname: Chen
mesh_terms: D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050784:Proto-Oncogene Protein c-ets-1 / Q000037:antagonists & inhibitors*; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004337:Drug Carriers; C494041:ETS1 protein, human; D058185:Magnetite Nanoparticles; D050784:Proto-Oncogene Protein c-ets-1; D044004:Xanthones; C052659:gambogic acid