Combined Applications of Repurposed Drugs and Their Detrimental Effects on Glioblastoma Cells.
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
Glioblastoma
/ drug therapy
Glycoproteins
/ genetics
Humans
Neoplasm Invasiveness
/ genetics
Neoplasm Recurrence, Local
/ drug therapy
Riluzole
/ administration & dosage
Temozolomide
/ administration & dosage
Tranylcypromine
/ administration & dosage
Valproic Acid
/ administration & dosage
Xenograft Model Antitumor Assays
Glioblastoma cells
cell death
combined treatment
proliferation
standard of care treatment
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
30
11
2018
revised:
13
12
2018
accepted:
14
12
2018
entrez:
29
12
2018
pubmed:
29
12
2018
medline:
8
1
2019
Statut:
ppublish
Résumé
Glioblastoma multiforme (GBM) is a malignant primary brain tumor with high rates of recurrence. This study aimed to investigate the effect of repurposed drug combinations on GBM. Viability of U87 MG and 11ST patient-derived GMB cell lines, after valproic acid, tranylcypromine or riluzole alone, in different combinations, as well as combined with standard temozolomide chemotherapy was examined using the MTT assay. Proliferation, mRNA level of tissue factor pathway inhibitor 2 (TFPI2), and cell invasion were evaluated using anti-Ki-67 antibody staining, reverse transcriptase-polymerase chain reaction and xCELLigence system. The strongest effect on cell viability was achieved by the combination of riluzole with valproic acid (U87MG: 27.2%, 11ST: 25.99%). Tranylcypromine significantly enhanced the effect of temozolomide when used in combination, as did valproic acid. The normally high proliferation of GBM significantly declined under treatment with valproic acid with tranylcypromine (p=0.01). Finally, we observed reduction of invasion comparing single tranylcypromine to its combination with valproic acid or riluzole. These results support the idea that combinations of drugs could increase the treatment efficiency of GBM.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Glioblastoma multiforme (GBM) is a malignant primary brain tumor with high rates of recurrence. This study aimed to investigate the effect of repurposed drug combinations on GBM.
MATERIALS AND METHODS
METHODS
Viability of U87 MG and 11ST patient-derived GMB cell lines, after valproic acid, tranylcypromine or riluzole alone, in different combinations, as well as combined with standard temozolomide chemotherapy was examined using the MTT assay. Proliferation, mRNA level of tissue factor pathway inhibitor 2 (TFPI2), and cell invasion were evaluated using anti-Ki-67 antibody staining, reverse transcriptase-polymerase chain reaction and xCELLigence system.
RESULTS
RESULTS
The strongest effect on cell viability was achieved by the combination of riluzole with valproic acid (U87MG: 27.2%, 11ST: 25.99%). Tranylcypromine significantly enhanced the effect of temozolomide when used in combination, as did valproic acid. The normally high proliferation of GBM significantly declined under treatment with valproic acid with tranylcypromine (p=0.01). Finally, we observed reduction of invasion comparing single tranylcypromine to its combination with valproic acid or riluzole.
CONCLUSION
CONCLUSIONS
These results support the idea that combinations of drugs could increase the treatment efficiency of GBM.
Identifiants
pubmed: 30591460
pii: 39/1/207
doi: 10.21873/anticanres.13099
doi:
Substances chimiques
Glycoproteins
0
tissue-factor-pathway inhibitor 2
0
Tranylcypromine
3E3V44J4Z9
Valproic Acid
614OI1Z5WI
Riluzole
7LJ087RS6F
Temozolomide
YF1K15M17Y
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
207-214Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.