期刊
MOLECULAR CANCER THERAPEUTICS
卷 14, 期 10, 页码 2279-2291出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-15-0201-T
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资金
- Department of Defense Breast Cancer Research Program (DOD BCRP) [W81 XWH-09-1-0058]
- Fulbright Visiting Scholar grant [1213204]
- Jane Coffin Childs Fund fellowship
- Cancer Research Institute
- Adelstein Fellowship
- Harvard Medical School MD/PhD Program
- Point Foundation
- Harvard CFAR scholar award
- DOD BCRP fellowship
- Swedish Research Council
Effective therapeutic strategies for in vivo siRNA delivery to knockdown genes in cells outside the liver are needed to harness RNA interference for treating cancer. EpCAM is a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells (TIC, also known as cancer stem cells). Here, we show that aptamer-siRNA chimeras (AsiC, an EpCAM aptamer linked to an siRNA sense strand and annealed to the siRNA antisense strand) are selectively taken up and knock down gene expression in EpCAM(+) cancer cells in vitro and in human cancer biopsy tissues. PLK1 EpCAM-AsiCs inhibit colony and mammosphere formation (in vitro TIC assays) and tumor initiation by EpCAM(+) luminal and basal-A triple-negative breast cancer (TNBC) cell lines, but not EpCAM(+) mesenchymal basal-B TNBCs, in nude mice. Subcutaneously administered EpCAM-AsiCs concentrate in EpCAM(+) Her2(+) and TNBC tumors and suppress their growth. Thus, EpCAM-AsiCs provide an attractive approach for treating epithelial cancer. (C) 2015 AACR.
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