Anti-EGFR antibody sensitizes colorectal cancer stem-like cells to Fluorouracil-induced apoptosis by affecting autophagy.
Anti-EGFR antibody sensitizes colorectal cancer stem-like cells to Fluorouracil-induced apoptosis by affecting autophagy.
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DOI：
10.18632/oncotarget.13233
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发表时间：
2016-12-06
期刊：
影响因子：
--
通讯作者：
Chen Z
中科院分区：
文献类型：
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作者：
Feng Y;Gao S;Gao Y;Wang X;Chen Z
最近的报告表明，结直肠癌（CRC）可能是由一小部分细胞（称为癌症干细胞（CSC））维持的，这些细胞具有耐药性，是化疗失败的关键原因。表皮生长因子受体（EGFR）控制CRC的发生和进展。针对EGFR的单克隆抗体（西妥昔单抗）已用于治疗几种癌症。然而，西妥昔单抗在CRC化疗中对CSC的影响尚不清楚。在这里，我们研究了西妥昔单抗对氟尿嘧啶（5-FU）处理的CRC细胞中CSC样细胞的影响。使用CD 133、CD 44或EphB 2-high作为标记物从CRC细胞独立地分离CSC样细胞，并通过肿瘤球形成测定法确认。我们发现5-FU增加了CSC样CRC细胞的凋亡。西妥昔单抗的共同应用增强了5-FU引起的CSC样CRC细胞的凋亡死亡，似乎是通过抑制5-FU诱导的CSC样CRC细胞中细胞自噬的增加。总之，我们的数据表明EGFR单克隆抗体可能通过影响自噬而使CSC样CRC细胞对5-FU诱导的凋亡敏感。
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.