[c-Myc regulation of ATP-binding cassette transporter reverses chemoresistance in CD133(+) colon cancer stem cells].
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.
Department of Radiotherapy, Lihuili Hospital of Ningbo Medical Center, Ningbo 315000, China. zhl520@163.com.
Huan-Le
HL
Zhang
Department of Biochemistry, Ningbo University School of Medicine, Ningbo 315000, China.
Ping
P
Wang
Department of Radiotherapy, Lihuili Hospital of Ningbo Medical Center, Ningbo 315000, China.
Miao-Zhen
MZ
Lu
Department of Radiotherapy, Lihuili Hospital of Ningbo Medical Center, Ningbo 315000, China.
San-Dian
SD
Zhang
D000071916:AC133 Antigen; D018528:ATP-Binding Cassette Transporters; D045744:Cell Line, Tumor; D003106:Colon; D015536:Down-Regulation; D006801:Humans; D014411:Neoplastic Stem Cells; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering
D000071916:AC133 Antigen; D018528:ATP-Binding Cassette Transporters; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering