EpCAM aptamer-mediated survivin silencing sensitized cancer stem cells to doxorubicin in a breast cancer model

Wang, Tao, Gantier, Michael P., Xiang, Dongxi, Bean, Andrew G., Bruce, Matthew, Zhou, Shu-Feng, Khasraw, Mustafa, Ward, Alister, Wang, Li, Wei, Ming Q., Al Shamaileh, Hadi, Chen, Lijue, She, Xiaodong, Lin, Jia, Kong, Lingxue, Shigdar, Sarah and Duan, Wei 2015, EpCAM aptamer-mediated survivin silencing sensitized cancer stem cells to doxorubicin in a breast cancer model, Theranostics, vol. 5, no. 12, pp. 1456-1472, doi: 10.7150/thno.11692.

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Title EpCAM aptamer-mediated survivin silencing sensitized cancer stem cells to doxorubicin in a breast cancer model
Author(s) Wang, Tao
Gantier, Michael P.
Xiang, Dongxi
Bean, Andrew G.
Bruce, Matthew
Zhou, Shu-Feng
Khasraw, MustafaORCID iD for Khasraw, Mustafa orcid.org/0000-0003-3249-9849
Ward, AlisterORCID iD for Ward, Alister orcid.org/0000-0001-7945-7975
Wang, Li
Wei, Ming Q.
Al Shamaileh, Hadi
Chen, Lijue
She, Xiaodong
Lin, Jia
Kong, LingxueORCID iD for Kong, Lingxue orcid.org/0000-0001-6219-3897
Shigdar, SarahORCID iD for Shigdar, Sarah orcid.org/0000-0001-8084-8447
Duan, WeiORCID iD for Duan, Wei orcid.org/0000-0001-5782-9184
Journal name Theranostics
Volume number 5
Issue number 12
Start page 1456
End page 1472
Total pages 17
Publisher Ivyspring International
Place of publication Wyoming, N.S.W.
Publication date 2015
ISSN 1838-7640
Keyword(s) Aptamer
Breast cancer
Cancer stem cell
RNA interference
Survivin
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
MAMMALIAN-CELLS
NEOADJUVANT CHEMOTHERAPY
TARGETING SURVIVIN
ADHESION MOLECULE
SIRNA DELIVERY
RNA APTAMER
THERAPEUTICS
EXPRESSION
CHEMOSENSITIVITY
IDENTIFICATION
Summary 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.
Language eng
DOI 10.7150/thno.11692
Field of Research 111504 Pharmaceutical Sciences
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Ivyspring International
Persistent URL http://hdl.handle.net/10536/DRO/DU:30080481

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