Aptamer-mediated survivin RNAi enables 5-fluorouracil to eliminate colorectal cancer stem cells.
Hadi AlShamailehTao WangDongxi XiangWang YinPhuong Ha-Lien TranRoberto A BarreroPei-Zhuo ZhangYong LiLingxue KongKe LiuShu-Feng ZhouYingchun HouSarah ShigdarWei DuanPublished in: Scientific reports (2017)
The development of chemoresistance and inability in elimination of cancer stem cells are among the key limitations of cancer chemotherapy. Novel molecular therapeutic strategies able to overcome such limitations are urgently needed for future effective management of cancer. In this report, we show that EpCAM-aptamer-guided survivin RNAi effectively downregulated survivin both in colorectal cancer cells in vitro and in a mouse xenograft model for colorectal cancer. When combined with the conventional chemotherapeutic agents, the aptamer-guided survivin RNAi was able to enhance the sensitivity towards 5-FU or oxaliplatin in colorectal cancer stem cells, increase apoptosis, inhibit tumour growth and improve the overall survival of mice bearing xenograft colorectal cancer. Our results indicate that survivin is one of the key players responsible for the innate chemoresistance of colorectal cancer stem cells. Thus, aptamer-mediated targeting of survivin in cancer stem cells in combination with chemotherapeutic drugs constitutes a new avenue to improve treatment outcome in oncologic clinics.
Keyphrases
- cancer stem cells
- gold nanoparticles
- sensitive detection
- papillary thyroid
- label free
- squamous cell
- primary care
- oxidative stress
- endoplasmic reticulum stress
- prostate cancer
- squamous cell carcinoma
- radiation therapy
- cell death
- current status
- lymph node metastasis
- skeletal muscle
- circulating tumor cells
- drug delivery
- signaling pathway
- adipose tissue
- robot assisted
- single molecule