Synergistic inhibition of tumor growth by combination treatment with drugs against different subpopulations of glioblastoma cells.
BMC Cancer
; 17(1): 905, 2017 12 29.
Article
em En
| MEDLINE
| ID: mdl-29284440
ABSTRACT
BACKGROUND:
Glioma stem cells (GSCs) contribute to tumor recurrence and drug resistance. This study characterizes the tumorigenesis of CD133+ cells and their sensitivity to pharmacological inhibition.METHODS:
GSCs from human U87 and rat C6 glioblastoma cell lines were isolated via magnetic cell sorting using CD133 as a cancer stem cell marker. Cell proliferation was determined using the WST-1 assay. An intracranial mouse model and bioluminescence imaging were used to assess the effects of drugs on tumor growth in vivo.RESULTS:
CD133+ cells expressed stem cell markers and exhibited self-renewal and enhanced tumor formation. Minocycline (Mino) was more effective in reducing the survival rate of CD133+ cells, whereas CD133- cells were more sensitive to inhibition by the signal transducer and activator of transcription 3 (STAT3) inhibitor. Inhibition of STAT3 decreased the expression of CD133+ stem cell markers. The combination of Mino and STAT3 inhibitor synergistically reduced the cell viability of glioma cells. Furthermore, this combination synergistically suppressed tumor growth in nude mice.CONCLUSION:
The results suggest that concurrent targeting of different subpopulations of glioblastoma cells may be an effective therapeutic strategy for patients with malignant glioma.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
/
Neoplasias Encefálicas
/
Glioblastoma
/
Sinergismo Farmacológico
/
Fator de Transcrição STAT3
/
Minociclina
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article