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

Jiujiao Gao; Qiu Yan; Shuai Liu; Xuesong Yang

doi:10.1371/journal.pone.0102590

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

PLoS One. 2014 Jul 14;9(7):e102590. doi: 10.1371/journal.pone.0102590. eCollection 2014.

Authors

Jiujiao Gao¹, Qiu Yan¹, Shuai Liu¹, Xuesong Yang¹

Affiliation

¹ Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, People's Republic of China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Neoplasm / genetics
Antigens, Neoplasm / metabolism
Antigens, Neoplasm / physiology*
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Breast Neoplasms / pathology
Caspase 3 / genetics
Caspase 3 / metabolism
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / metabolism
Cell Adhesion Molecules / 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
bcl-2-Associated X Protein / metabolism

Substances

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

Grants and funding

This work was supported by grants from the Major State basic Research Development Program of China (2012CB822103), the National Natural Science Foundation of China (No.: 30800195, 31070729 and 31270866) and the National Natural Science Foundation of Liaoning Province (NO.2013023046). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.