Comparison of Inhibitory Effect of 17-DMAG Nanoparticles and Free 17-DMAG in HSP90 Gene Expression in Lung Cancer

Background: Up-regulation of hsp90 gene expression occurs in numerous cancers such as lung cancer.D,L-lactic-co-glycolic acid-poly ethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin(PLGA-PEG-17DMAG) complexes and free 17-DMAG may inhibit the expression. The purpose of this studywas to examine whether nanocapsulating 17DMAG improves the anti cancer effect over free 17DMAG in theA549 lung cancer cell line. Materials and
Methods: Cells were grown in RPMI 1640 supplemented with 10%FBS. Capsulation of 17DMAG is conducted through double emulsion, then the amount of loaded drug wascalculated. Other properties of this copolymer were characterized by Fourier transform infrared spectroscopyand H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity on the grown of lung cancercell line was carried out through MTT assay. After treatment, RNA was extracted and cDNA was synthesized.In order to assess the amount of hsp90 gene expression, real-time PCR was performed.
Results: In regard to theamount of the drug load, IC50 was significant decreased in nanocapsulated(NC) 17DMAG in comparison withfree 17DMAG. This was confirmed through decrease of HSP90 gene expression by real-time PCR.
Conclusions:The results demonstrated that PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG indown-regulating of hsp90 expression by enhancing uptake by cells. Therefore, PLGA-PEG could be a superiorcarrier for this kind of hydrophobic agent.