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http://dx.doi.org/10.7314/APJCP.2014.15.17.7113

Comparison of Inhibitory Effects of 17-AAG Nanoparticles and Free 17-AAG on HSP90 Gene Expression in Breast Cancer  

Ghalhar, Masoud Gandomkar (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences)
Akbarzadeh, Abolfazl (Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences)
Rahmati, Mohammad (Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences)
Mellatyar, Hassan (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences)
Dariushnejad, Hassan (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences)
Zarghami, Nosratallah (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences)
Barkhordari, Amin (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.17, 2014 , pp. 7113-7118 More about this Journal
Abstract
Background: HSP90 may be overexpressed in cancer cells which are greatly dependent on Hsp90 function. Geldanamycin derivative 17 allylamino-17-demethoxygeldanamycin (17-AAG) inhibits the function and expression of HSP90. 17-AAG has poor water-solubility which is a potential problem for clinical practice. In this study for improving the stability and solubility of molecules in drug delivery systems we used a ${\beta}$-cyclodextrin-17AAG complex. Materials and Methods: To assess cytotoxic effects of ${\beta}$-cyclodextrin-17AAG complexes and free 17AAG, colorimetric cell viability (MTT) assays were performed. Cells were treated with equal concentrations of ${\beta}$-cyclodextrin- 17AAG complex and free 17AAG and Hsp90 gene expression levels in the two groups was compared by real-time PCR. Results: MTT assay confirmed that ${\beta}$-cyclodextrin- 17AAG complex enhanced 17AAG cytotoxicity and drug delivery in T47D breast cancer cells. The level of Hsp90 gene expression in cells treated with ${\beta}$-cyclodextrin- 17AAG complex was lower than that of cells treated with free 17AAG (P=0.001). Conclusions: The results demonstrated that ${\beta}$-cyclodextrin- 17AAG complexes are more effective than free 17AAG in down-regulating HSP90 expression due to enhanced ${\beta}$-cyclodextrin-17AAG uptake by cells. Therefore, ${\beta}$-cyclodextrin could be superior carrier for this kind of hydrophobic agent.
Keywords
${\beta}$-cyclodextrin; geldanamycin; cytotoxic effects; MTT assay; uptake;
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