EpCAM Aptamer-mediated Survivin Silencing Sensitized Cancer Stem Cells to Doxorubicin in a Breast Cancer Model.

Published online

Journal Article

Understanding the molecular basis of drug resistance and utilising this information to overcome chemoresistance remains a key challenge in oncology. Here we report that survivin, a key protein implicated in drug resistance, is overexpressed in cancer stem cell pool of doxorubicin-resistant breast cancer cells. Moreover, by utilising an active targeting system consisting of an RNA aptamer targeted against the epithelial cell adhesion molecule and a Dicer substrate survivin siRNA, we could deliver a high dose of the siRNA to cancer stem cells in xenograft tumours. Importantly, silencing of survivin with this aptamer-siRNA chimera in cancer stem cell population led to the reversal of chemoresistance, such that combined treatment with low dose of doxorubicin inhibited stemness, eliminated cancer stem cells via apoptosis, suppressed tumour growth, and prolonged survival in mice bearing chemoresistant tumours. This strategy for in vivo cancer stem cell targeting has wide application for future effective silencing of anti-death genes and in fact any dysregulated genes involved in chemoresistance and tumour relapse.

Full Text

Duke Authors

Cited Authors

  • Wang, T; Gantier, MP; Xiang, D; Bean, AG; Bruce, M; Zhou, S-F; Khasraw, M; Ward, A; Wang, L; Wei, MQ; AlShamaileh, H; Chen, L; She, X; Lin, J; Kong, L; Shigdar, S; Duan, W

Published Date

  • 2015

Published In

Volume / Issue

  • 5 / 12

Start / End Page

  • 1456 - 1472

PubMed ID

  • 26681989

Pubmed Central ID

  • 26681989

Electronic International Standard Serial Number (EISSN)

  • 1838-7640

Digital Object Identifier (DOI)

  • 10.7150/thno.11692

Language

  • eng

Conference Location

  • Australia