c-Myc regulation of ATP-binding cassette transporter reverses chemoresistance in CD133(+) colon cancer stem cells.
- Author:
Huan-Le ZHANG
1
;
Ping WANG
2
;
Miao-Zhen LU
3
;
San-Dian ZHANG
3
Author Information
1. Department of Radiotherapy, Lihuili Hospital of Ningbo Medical Center, Ningbo 315000, China. zhl520@163.com.
2. Department of Biochemistry, Ningbo University School of Medicine, Ningbo 315000, China.
3. Department of Radiotherapy, Lihuili Hospital of Ningbo Medical Center, Ningbo 315000, China.
- Publication Type:Journal Article
- MeSH:
AC133 Antigen;
ATP-Binding Cassette Transporters;
Cell Line, Tumor;
Colon;
Down-Regulation;
Humans;
Neoplastic Stem Cells;
Proto-Oncogene Proteins c-myc;
RNA, Small Interfering
- From:
Acta Physiologica Sinica
2016;68(2):171-178
- CountryChina
- Language:Chinese
-
Abstract:
The present study was aimed to explore the role of c-Myc gene regulation in maintaining the self-renewal and drug-resistant properties of colon cancer stem cells (CSCs) and the underlying mechanism. CD133(+) cells were isolated by flow cytometry cell sorting from human HT29 cancer cells. A small interfering RNA (siRNA) against c-Myc was used, and the mRNA and protein expressions of c-Myc were investigated by real-time PCR and Western blotting, respectively. To evaluate the effect of c-Myc on the drug resistance of colon CSCs, CD133(+) cells transfected with c-Myc-siRNA were exposed to 5-FU, oxaliplatin, or their combination. The expressions of ATP-binding cassette (ABC) transporters, including ABCG2, ABCB5 and MDR-1, were detected by Western blotting. The results showed that c-Myc was highly expressed in CD133(+) colon CSCs, and the protein and mRNA expressions of c-Myc were effectively blocked by c-Myc siRNA. Furthermore, CD133(+) cells showed significantly increased survival rate in chemotherapy treatment, compared with CD133(-) cells. c-Myc silencing sensitized CD133(+) cells to chemotherapy-induced cytotoxicity and down-regulated the protein expression levels of ABCG2, MDR-1 and ABCB5. These results suggest c-Myc silencing may regulate the expressions of ABC transporters in colon CSCs, and enhance the sensitivity of CSCs to the chemotherapy.
