• Targeting genes of Hsp90 and hTERT by 17-DMAG loaded PLA/PEG electrospun nanofibrous scaffolds in T47D breast cancer cells
  • Hasan Mellatyar,1,* Sona Talaei,2
    1. Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
    2. Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran


  • Introduction: Up-regulation of Hsp90 and hTERT genes takes place in breast cancer cells, and their targeting may be a promising step in breast cancer therapy. In this study, poly(lactide)-poly(ethylene glycol) (PLA-PEG) nanofibers loaded with 17-dimethylaminoethylamino-17-demethoxy geldanamycin (17-DMAG) were designed to increase the anti-cancer effect of 17-DMAG.
  • Methods: For this purpose, 17-DMAG-loaded PLA-PEG nanofibers were successfully fabricated via electrospinning technique and characterized using Field Emission Scanning Electron Microscopy (FE-SEM) and Fourier Transform Infrared (FTIR). Colorimetric MTT metabolic activity assay was used to determine the drug cytotoxicity. Also, the expression levels of the Hsp90 gene in the T47D cells seeded on the scaffolds were assessed using real-time RT-PCR. The effect of 17-DMAG and 17-DMAG loaded PLA-PEG nanofiber treatment on telomerase activity was monitored by TRAP assay.
  • Results: Taking into account drug load, IC50 has significantly reduced in 17-DMAG-loaded PLA-PEG nanofibers than free 17-DMAG. This finding was associated with a decrease in Hsp90 gene expression and telomerase activity.
  • Conclusion: 17-DMAG-loaded PLA-PEG nanofibers can be more effective than free 17-DMAG in down-regulating the Hsp90 expression and inhibiting the activity of telomerase, at the same time exerting more potent cytotoxic effects. Therefore, PLA-PEG can be a superior carrier for this type of hydrophobic agent.
  • Keywords: Breast Cancer, Hsp90, 17-DMAG, PLA/PEG nanofiber, hTERT.