A novel therapeutic drug for colon cancer: EpCAM scFv-truncated protamine (tp)-siRNA

• Published in: Cell biology international 2013-08, Vol.37 (8), p.860-864
• Main Authors: Hao, Huiwen, Zhen, Yansen, Wang, Zaicun, Chen, Fulin, Xie, Xin
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; cancer therapy; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; colon cancer; Colonic Neoplasms - metabolism; Colonic Neoplasms - therapy; EpCAM; Epithelial Cell Adhesion Molecule; Gene Knockdown Techniques - methods; Genetic Therapy - methods; Humans; Peptide Fragments - chemistry; Protamines - chemistry; Protein Binding; RNA, Small Interfering - genetics; Single-Chain Antibodies - chemistry; siRNA; Transfection - methods; tumor antigen; Wnt Signaling Pathway - genetics; Wnt/β-catenin
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.10112

Colon cancer is a type of malignant tumor that causes considerable mortality worldwide. Epithelial cellular adhesion molecule (EpCAM), a tumor‐associated antigen of colon tumors, is a target for colon cancer therapy. EpCAM‐specific monoclonal antibodies (mAbs) have been applied in human colon cancer since the 1990s; however, the therapeutic effects are limited. EpCAM activates nuclear signaling pathways by releasing its intracellular domain (EpICD). The released EpICD stimulates the Wnt/β‐catenin signaling pathway, which is also strongly associated with tumorigenesis. EpCAM is also a target gene of the Wnt/β‐catenin signaling pathway. EpCAM and the Wnt/β‐catenin signaling pathway form a functional interaction cycle in colon cancer. Thus, we propose a new therapeutic drug for colon cancer: an EpCAM single‐chain fragment variable antibody (scFv)‐truncated protamine‐siRNA. EpCAM scFv can recognize and bind colon cancer cells through its EpCAM antigen activity. Furthermore, the specific siRNA transferred into colon cancer cells specifically inhibits Wnt/β‐catenin signal transmission. Therefore, this new drug may efficiently interrupt the functional cycle between EpCAM and Wnt/β‐catenin signaling and be an effective therapeutic strategy for colon cancer.