2021

BMC Cancer

Rocznik: 2021 | Tom: 21 | Numer: 1

artykuł naukowy

angielski

EN Background:Glioblastoma (GBM) is the deadliest and the most common primary brain tumor in adults. Theinvasiveness and proliferation of GBM cells can be decreased through the inhibition of Wnt/β-catenin pathway. Inthis regard, celecoxib is a promising agent, but other COXIBs and 2,5-dimethylcelecoxib (2,5-DMC) await elucidation.Thus, the aim of this study was to analyze the impact of celecoxib, 2,5-DMC, etori-, rofe-, and valdecoxib on GBMcell viability and the activity of Wnt/β-catenin pathway. In addition, the combination of the compounds withtemozolomide (TMZ) was also evaluated. Cell cycle distribution and apoptosis,MGMTmethylation level, COX-2 andPGE2 EP4 protein levels were also determined in order to better understand the molecular mechanisms exerted bythese compounds and to find out which of them can serve best in GBM therapy.Methods:Celecoxib, 2,5-DMC, etori-, rofe- and valdecoxib were evaluated using three commercially available andtwo patient-derived GBM cell lines. Cell viability was analyzed using MTT assay, whereas alterations inMGMTmethylation level were determined using MS-HRM method. The impact of COXIBs, in the presence and absenceof TMZ, on Wnt pathway was measured on the basis of the expression ofβ-catenin target genes. Cell cycledistribution and apoptosis analysis were performed using flow cytometry. COX-2 and PGE2 EP4 receptor expressionwere evaluated using Western blot analysis.Results:Wnt/β-catenin pathway was attenuated by COXIBs and 2,5-DMC irrespective of the COX-2 expressionprofile of the treated cells, theirMGMTmethylation status, or radio/chemoresistance. Celecoxib and 2,5-DMC werethe most cytotoxic. Cell cycle distribution was altered, and apoptosis was induced after the treatment withcelecoxib, 2,5-DMC, etori- and valdecoxib in T98G cell line. COXIBs and 2,5-DMC did not influenceMGMTmethylation status, but inhibited COX-2/PGE2/EP4 pathway.Conclusions:Not only celecoxib, but also 2,5-DMC, etori-, rofe- and valdecoxib should be further investigated aspotential good anti-GBM therapeutics.

493

10.1186/s12885-021-08164-1

https://link.springer.com/content/pdf/10.1186/s12885-021-08164-1.pdf

CC BY-ND (uznanie autorstwa - bez utworów zależnych)

ostateczna wersja opublikowana

05.2021

w momencie opublikowania

100

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