Abstract

Objective To investigate the effect of sesquiterpene lactone derivative (ACT001) on the neurosphere formation and stemness maintenance of U87-MG glioma stem cells. Methods Bioinformatics was used to analyze the relationship between STAT3 mRNA and different grades of human glioma as well as the overall survival in 1 477 glioma patients in CGGA, TCGA, and GEO (GSE4290, GSE16011) databases. Magnetic activated cell sorting method was used to obtain CD133-positive U87-MG cells. The effect of ACT001 on the survival viability of U87-MG GSCs was detected via Cell Counting Kit-8 (CCK-8). The effect of ACT001 on the ability of neurosphere formation was observed by single-cell neurosphere formation assay. Immunofluorescence staining was used to measure the effect of ACT001 on stem cells markers (CD133、CD44 and Nestin) in neurospheres of U87-MG GSCs. The expressions of STAT3, p-STAT3, CD44 and CD133 were detected using western blot after treatment of ACT001. Results Bioinformatics analysis showed that as the grades of glioma increased, the expression of STAT3 mRNA also increased (all P 0.05), while the protein expression of p-STAT3 was decreased through assessment by Western blot (all P<0.01). Conclusion ACT001 could suppress the neurosphere formation ability and reduce the stemness maintenance in U87-MG glioma stem cells by inhibiting STAT3 signaling pathway. Key words: Glioma; Neoplastic stem cells; Sesquiterpene lactone derivative; STAT3 signaling pathway

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