Synergistic inhibition of tumor growth by combination treatment with drugs against different subpopulations of glioblastoma cells.

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.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Chang CH,Liu WT,Hung HC,Gean CY,Tsai HM,Su CL,Gean PW

doi

10.1186/s12885-017-3924-y

subject

Has Abstract

pub_date

2017-12-29 00:00:00

pages

905

issue

1

issn

1471-2407

pii

10.1186/s12885-017-3924-y

journal_volume

17

pub_type

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