Gambogic acid-loaded magnetic Fe3O4 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 Fe3O4 nanoparticles (GA-MNP-Fe3O4) on the suppression of ETS1-mediated cell proliferation and migration in Panc-1 pancreatic cancer cells. Methods: The effects caused by GA-MNP-Fe3O4 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-Fe3O4 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-Fe3O4 nanoparticles targeting ETS1 should be considered as a promising contribution for better pancreatic cancer care. © 2012 Wang et al.