Targeting HSP90 Gene Expression with 17-DMAG Nanoparticles in Breast Cancer Cells.

Abstract

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.

MATERIALS AND 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.

• Authors: Hassan Mellatyar, Sona Talaei, Kazem Nejati-Koshki, Abolfazl Akbarzadeh
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 17 Issue 5 Pg. 2453-7 ( 2016) ISSN: 2476-762X [Electronic] Thailand
• PMID: 27268613 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Benzoquinones
• Drug Carriers
• HSP90 Heat-Shock Proteins
• Lactams, Macrocyclic
• RNA, Messenger
• 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Benzoquinones (chemistry, pharmacology)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Cell Proliferation (drug effects)
• Drug Carriers
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• HSP90 Heat-Shock Proteins (antagonists & inhibitors, genetics, metabolism)
• Humans
• Lactams, Macrocyclic (chemistry, pharmacology)
• Nanoparticles (administration & dosage, chemistry)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Spectroscopy, Fourier Transform Infrared
• Tumor Cells, Cultured