c-Myc regulation of ATP-binding cassette transporter reverses chemoresistance in CD133(+) colon cancer stem cells / 生理学报
Acta Physiologica Sinica
;
(6): 171-178, 2016.
Artículo
en Chino
| WPRIM
| ID: wpr-331669
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.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Células Madre Neoplásicas
/
Regulación hacia Abajo
/
Proteínas Proto-Oncogénicas c-myc
/
Colon
/
Transportadoras de Casetes de Unión a ATP
/
ARN Interferente Pequeño
/
Línea Celular Tumoral
/
Antígeno AC133
Límite:
Humanos
Idioma:
Chino
Revista:
Acta Physiologica Sinica
Año:
2016
Tipo del documento:
Artículo
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