2,6-DMBQ is a novel mTOR inhibitor that reduces gastric cancer growth in vitro and in vivo.
Animals
Apoptosis
Benzoquinones
/ pharmacology
Biomarkers, Tumor
Cell Cycle
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
In Vitro Techniques
Mice
Mice, Nude
Prognosis
Protein Kinase Inhibitors
/ pharmacology
Stomach Neoplasms
/ drug therapy
TOR Serine-Threonine Kinases
/ antagonists & inhibitors
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
2,6-DMBQ
Gastric cancer
Patient-derived xenograft
mTOR
p70S6K
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
09 Jun 2020
09 Jun 2020
Historique:
received:
22
02
2020
accepted:
28
05
2020
entrez:
11
6
2020
pubmed:
11
6
2020
medline:
5
2
2021
Statut:
epublish
Résumé
Fermented wheat germ extract has been reported to exert various pharmacological activities, including anti-oxidant, anti-cell growth and cell apoptosis in various cancer cells. Although 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) is a benzoquinone compound and found in fermented wheat germ extract, its anticancer effects and molecular mechanism(s) against gastric cancer have not been investigated. Anticancer effects of 2,6-DMBQ were determined by MTT, soft agar, cell cycle and Annexin V analysis. Potential candidate proteins were screened via in vitro kinase assay and Western blotting. mTOR knockdown cell lines were established by lentiviral infection with shmTOR. The effect of 2,6-DMBQ on tumor growth was assessed using gastric cancer patient-derived xenograft models. 2,6-DMBQ significantly reduced cell growth and induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells. 2,6-DMBQ reduced the activity of mTOR in vitro. The inhibition of cell growth by 2,6-DMBQ is dependent upon the expression of the mTOR protein. Remarkably, 2,6-DMBQ strongly reduced patient-derived xenograft gastric tumor growth in an in vivo mouse model. 2,6-DMBQ is an mTOR inhibitor that can be useful for treating gastric cancer. It has therapeutic implications for gastric cancer patients.
Sections du résumé
BACKGROUND
BACKGROUND
Fermented wheat germ extract has been reported to exert various pharmacological activities, including anti-oxidant, anti-cell growth and cell apoptosis in various cancer cells. Although 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) is a benzoquinone compound and found in fermented wheat germ extract, its anticancer effects and molecular mechanism(s) against gastric cancer have not been investigated.
METHODS
METHODS
Anticancer effects of 2,6-DMBQ were determined by MTT, soft agar, cell cycle and Annexin V analysis. Potential candidate proteins were screened via in vitro kinase assay and Western blotting. mTOR knockdown cell lines were established by lentiviral infection with shmTOR. The effect of 2,6-DMBQ on tumor growth was assessed using gastric cancer patient-derived xenograft models.
RESULTS
RESULTS
2,6-DMBQ significantly reduced cell growth and induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells. 2,6-DMBQ reduced the activity of mTOR in vitro. The inhibition of cell growth by 2,6-DMBQ is dependent upon the expression of the mTOR protein. Remarkably, 2,6-DMBQ strongly reduced patient-derived xenograft gastric tumor growth in an in vivo mouse model.
CONCLUSIONS
CONCLUSIONS
2,6-DMBQ is an mTOR inhibitor that can be useful for treating gastric cancer. It has therapeutic implications for gastric cancer patients.
Identifiants
pubmed: 32517736
doi: 10.1186/s13046-020-01608-9
pii: 10.1186/s13046-020-01608-9
pmc: PMC7285595
doi:
Substances chimiques
Benzoquinones
0
Biomarkers, Tumor
0
Protein Kinase Inhibitors
0
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
2,6-dimethyl-1,4-benzoquinone
HET5TF8ZGO
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107Subventions
Organisme : Henan Joint Fund
ID : U1804196
Organisme : National Natural Science Foundation China
ID : 81572812
Organisme : Key program of Henan Province, China
ID : 161100510300
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