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

Publish Year: 1394
نوع سند: مقاله کنفرانسی
زبان: English
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شناسه ملی سند علمی:

ICBCMED11_096

تاریخ نمایه سازی: 21 اردیبهشت 1397

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 β-cyclodextrin- 17AAG complex. Materials and Methods: To assess cytotoxic effects of β-cyclodextrin- 17AAG complexes and free 17AAG, colorimetric cell viability (MTT) assays were performed. Cells were treated with equal concentrations of β- 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 β-cyclodextrin- 17AAG complex enhanced 17AAG cytotoxicity and drug delivery in T47D breast cancer cells. The level of Hsp90 gene expression in cells treated with β- cyclodextrin- 17AAG complex was lower than that of cells treated with free 17AAG (P=0.001). Conclusions: The results demonstrated that β-cyclodextrin- 17AAG complexes are more effective than free 17AAG in down-regulating HSP90 expression due to enhanced β-cyclodextrin-17AAG uptake by cells. Besides, β-Cyclodextrin-17AAG complex has fewer side effects than 17AAG free and has more inhibitory effect on hsp90 expression and function; consequently we can use this complex as a new anticancer compound in breast cancer treatment. Therefore, β-cyclodextrin could be superior carrier for this kind of hydrophobic agent.

Keywords:

β-cyclodextrin - geldanamycin - cytotoxic effects - MTT assay – uptake

Authors

Roghayeh Sheervalilou

Department of Molecular medicine, Faculty of Medical Advanced Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

Masoud Gandomkar Ghalhar

Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

Rana Farajzadeh

Department of Genetic, Tabriz Branch, Islamic Azad University, Tabriz, Iran

Farajzadeh Zarghami

Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran