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 study was to examine whether nanocapsulating 17DMAG improves the anti cancer effect over free 17DMAG in the A549 lung cancer cell line.


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 was calculated. Other properties of this copolymer were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity on the grown of lung cancer cell 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 the amount of the drug load, IC50 was significant decreased in nanocapsulated(NC) 17DMAG in comparison with free 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 in down-regulating of hsp90 expression by enhancing uptake by cells. Therefore, PLGA-PEG could be a superior carrier for this kind of hydrophobic agent.
Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran E-mail : zarghami@tbzmed.ac.ir.
Hassan
H
Mellatyar
Abolfazl
A
Akbarzadeh
Mohammad
M
Rahmati
Masoud Gandomkar
MG
Ghalhar
Ali
A
Etemadi
Kazem
K
Nejati-Koshki
Nosratallah
N
Zarghami
Amin
A
Barkhordari
D016227:Benzoquinones / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D053758:Nanoparticles; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D004337:Drug Carriers; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C448659:17-(dimethylaminoethylamino)-17-demethoxygeldanamycin