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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)
  • Published : 2014.09.15

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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