Anti-EGFR antibody sensitizes colorectal cancer stem-like cells to Fluorouracil-induced apoptosis by affecting autophagy
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Ye Feng1, Shuohui Gao1, Yongjian Gao1, Xuefeng Wang1, Zhi Chen2
1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China
2Department of Nephrology, First Hospital of Jilin University, Changchun 130021, China
Zhi Chen, email: [email protected]
Keywords: colorectal carcinoma (CRC), cancer stem cells (CSCs), CD133, CD44, EphB2
Received: June 29, 2016 Accepted: October 27, 2016 Published: November 09, 2016
Recent reports suggest that colorectal carcinoma (CRC) may be sustained by a small subpopulation of cells, termed cancer stem cells (CSCs), which have drug resistance properties as a key reason for chemotherapy failure. The epidermal growth factor receptor (EGFR) controls CRC initiation and progression. Monoclonal antibody against EGFR (cetuximab) has been used in treatment of several cancers. However, the effects of cetuximab on CSCs in the CRC chemotherapy remain unclear. Here, we studied the effects of cetuximab on the CSC-like cells in Fluorouracil (5-FU)-treated CRC cells. CSC-like cells were independently isolated from CRC cells using CD133, CD44 or EphB2-high as markers and confirmed by tumor sphere formation assay. We found that 5-FU increased the apoptotic death of CSC-like CRC cells. Co-application of cetuximab augmented the apoptotic death of CSC-like CRC cells by 5-FU, seemingly through inhibition of 5-FU-induced increases in cell autophagy in CSC-like CRC cells. Together, our data suggest that EGFR monoclonal antibody may sensitize CSC-like CRC cells to 5-FU-induced apoptosis by affecting autophagy.
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