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Gambogic acid-loaded magnetic Fe(3)O(4) nanoparticles inhibit Panc-1 pancreatic cancer cell proliferation and migration by inactivating transcription factor ETS1.

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsCailian Wang, Haijun Zhang, Yan Chen, Fangfang Shi, Baoan Chen
JournalInternational journal of nanomedicine (Int J Nanomedicine) Vol. 7 Pg. 781-7 ( 2012) ISSN: 1178-2013 [Electronic] New Zealand
PMID22393285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drug Carriers
  • ETS1 protein, human
  • Magnetite Nanoparticles
  • Proto-Oncogene Protein c-ets-1
  • Xanthones
  • gambogic acid
Topics
  • Cell Growth Processes (drug effects)
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Cell Survival (drug effects)
  • Drug Carriers (chemistry, pharmacology)
  • Humans
  • Magnetite Nanoparticles (chemistry)
  • Pancreatic Neoplasms (drug therapy, metabolism, pathology)
  • Proto-Oncogene Protein c-ets-1 (antagonists & inhibitors)
  • Xanthones (chemistry, pharmacology)

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