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

Area of Science:

• Oncology
• Molecular Biology
• Biotechnology

Background:

• Chemoresistance is a major obstacle in cancer treatment.
• Survivin, a protein linked to drug resistance, is overexpressed in cancer stem cells (CSCs) of doxorubicin-resistant breast cancer.
• Targeting CSCs is crucial for effective cancer therapy.

Purpose of the Study:

• To develop a targeted delivery system for survivin siRNA to CSCs.
• To investigate if survivin silencing can reverse chemoresistance in breast cancer.
• To evaluate the efficacy of combined therapy in preclinical models.

Main Methods:

• An active targeting system was created using an RNA aptamer against epithelial cell adhesion molecule and a Dicer substrate survivin siRNA.
• This aptamer-siRNA chimera was used to deliver survivin siRNA to CSCs in xenograft tumors.
• The effects of survivin silencing and combined doxorubicin treatment on CSCs, tumor growth, and survival were assessed.

Main Results:

• High-dose survivin siRNA was successfully delivered to CSCs in vivo.
• Survivin silencing in CSCs reversed chemoresistance.
• Combined treatment with low-dose doxorubicin and the aptamer-siRNA chimera inhibited stemness, induced CSC apoptosis, suppressed tumor growth, and prolonged survival in mice.

Conclusions:

• Targeted delivery of survivin siRNA to CSCs can overcome chemoresistance in breast cancer.
• This strategy effectively eliminates CSCs and inhibits tumor progression.
• The developed in vivo CSC targeting system has broad potential for silencing genes involved in chemoresistance and tumor relapse.