Knockdown of EpCAM enhances the chemosensitivity of breast cancer cells to 5-fluorouracil by downregulating the antiapoptotic factor Bcl-2.

Abstract

Resistance to fluoropyrimidine-based chemotherapy is the main reason for the failure of cancer treatment, and drug resistance is associated with an inability of tumor cells to undergo apoptosis in response to treatment. Alterations in the expression of epithelial cell adhesion molecule (EpCAM) affect the sensitivity or resistance of tumor cells to anticancer treatment and the activity of intracellular signaling pathways. However, the role of EpCAM in the induction of apoptosis in breast cancer cells remains unclear. Here, we investigated the effect of EpCAM gene knockdown on chemosensitivity to 5-fluorouracil (5-FU) in MCF-7 cells and explored the underlying mechanisms. Our results showed that knockdown of EpCAM promoted apoptosis, inhibited cell proliferation and caused cell-cycle arrest. EpCAM knockdown enhanced the cytotoxic effect of 5-FU, promoting apoptosis by downregulating the expression of the anti-apoptotic protein Bcl-2 and upregulating the expression of the pro-apoptotic proteins Bax, and caspase3 via the ERK1/2 and JNK MAPK signaling pathways in MCF-7 cells. These results indicate that knockdown of EpCAM may have a tumor suppressor effect and suggest EpCAM as a potential target for the treatment of breast cancer.

• Authors: Jiujiao Gao, Qiu Yan, Shuai Liu, Xuesong Yang
• Journal: PloS one (PLoS One) Vol. 9 Issue 7 Pg. e102590 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25019346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• BAX protein, human
• Cell Adhesion Molecules
• Epithelial Cell Adhesion Molecule
• bcl-2-Associated X Protein
• Caspase 3
• Fluorouracil

Topics

• Antigens, Neoplasm (genetics, metabolism, physiology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (pathology)
• Caspase 3 (genetics, metabolism)
• Cell Adhesion Molecules (genetics, metabolism, physiology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Down-Regulation
• Drug Resistance, Neoplasm (genetics)
• Epithelial Cell Adhesion Molecule
• Female
• Fluorouracil (pharmacology)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• MAP Kinase Signaling System
• MCF-7 Cells
• Signal Transduction
• bcl-2-Associated X Protein (genetics, metabolism)