Targeting HSP90 Gene Expression with 17-DMAG Nanoparticles in Breast Cancer Cells.
BACKGROUND
Dysregulation of HSP90 gene expression is known to take place in breast cancer. Here we used D,L-lactic-co-glycolic acid-polyethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG to inhibit the expression of HSP90 gene in the T47D breast cancer cell line. The purpose was to determine whether nanoencapsulating 17DMAG improves the anti-cancer effects as compared to free 17DMAG.


METHODS
The T47D breast cancer cell line was grown in RPMI 1640 supplemented with 10% FBS. Encapsulation of 17DMAG was conducted through a double emulsion method and properties of copolymers were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity was by MTT assay. After treatment of T47D cells with a given amount of drug, RNA was extracted and cDNA was synthesized. In order to assess HSP90 gene expression, real-time PCR was performed.


RESULTS
Taking into account drug load, IC50 was significant decreased in nanocapsulated 17DMAG in comparison with free 17DMAG. This finding was associated with decrease of HSP90 gene expression.


CONCLUSIONS
PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of HSP90 expression, at the saesm time exerting more potent cytotoxic effects. Therefore, PLGA-PEG could be a superior carrier for this type of hydrophobic agent.
Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran E-mail : akbarzadehab@tbzmed.ac.ir.
Hassan
H
Mellatyar
Sona
S
Talaei
Kazem
K
Nejati-Koshki
Abolfazl
A
Akbarzadeh
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000494:pharmacology*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017550:Spectroscopy, Fourier Transform Infrared; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016227:Benzoquinones; D004337:Drug Carriers; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D012333:RNA, Messenger; C448659:17-(dimethylaminoethylamino)-17-demethoxygeldanamycin