eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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SCImago Journal & Country Rank
4/2019
vol. 15
 
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abstract:
Basic research

Microarray gene profiling analysis of glioblastoma cell line U87 reveals suppression of the FANCD2/Fanconi anemia pathway by the combination of Y15 and temozolomide

Zichuan Wang, Nan Chen, Jin Yang, Qingzhong Wang, Aimin Li

Arch Med Sci 2019; 15 (4): 1035–1046
Online publish date: 2019/06/20
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Introduction
A recent study showed that a combination of Y15 (a FAK autophosphorylation inhibitor) with temozolomide (TMZ) treatment was effective in glioblastoma (GBM) therapy. In this study, we further investigated the pathways and genes that are differentially expressed in Y15 and TMZ treated U87 cells via bioinformatics analysis.

Material and methods
The microarray gene profiling analysis screened out genes with differential expression in U87 cells treated with TMZ and Y15. Gene set enrichment analysis (GSEA) identified the key GO terms and KEGG pathways in TMZ + Y15 treated U87 cells. The functional partner genes of TMZ were predicted by the STICH database. FANCD2 expression in U87 cells was detected by qRT-PCR. MTT assay and colony formation assay were conducted for cell viability detection, and flow cytometry was performed for cell apoptosis detection. Western blot was conducted to determine the expression levels of the downstream proteins of the Fanconi anemia (FA) pathway, FAN1 and BRCA2.

Results
The FA pathway was suppressed in U87 cells after treatment with TMZ and Y15. Genes involved in this pathway, including FANCD2, were also down-regulated. FANCD2 knockdown could restrain viability and promote apoptosis of U87 cells, as well as enhancing the inhibitory effect of TMZ + Y15 treatment. FANCD2 could regulate the FA pathway as the protein expression levels of FAN1 and BRCA2 were modulated by FANCD2.

Conclusions
The FA pathway and FANCD2 are down-regulated in U87 cells treated with TMZ and Y15. FANCD2 down-regulation by TMZ + Y15 treatment suppressed growth of U87 cells through inhibiting the FA pathway.

keywords:

glioblastoma, FANCD2, Fanconi anemia pathway, temozolomide, Y15, gene set enrichment analysis

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