Sophoridine exerts tumor-suppressive activities via promoting ESRRG-mediated ß-catenin degradation in gastric cancer.
BMC Cancer
; 20(1): 582, 2020 Jun 22.
Article
em En
| MEDLINE
| ID: mdl-32571331
ABSTRACT
BACKGROUND:
As a natural alkaloid product isolated from Sophora alopecuroides. L, Sophoridine reshapes gastric cancer immune microenvironment via inhibiting chemotaxis and M2 polarization of tumor-associated macrophages (TAMs). However, the exact effects and underlying mechanism of Sophoridine on gastric cancer cells remains poorly known.METHODS:
The potential anti-tumor effects of Sophoridine on gastric cancer cell lines, including AGS and SGC7901 cells, were detected by CCK-8, EDU and colony forming assay, immunofluorescence, transwell assay, and flow cytometry. Molecular mechanisms of Sophoridine were investigated by siRNA transfection, nuclear/cytoplasmic extraction and western blot. The synergistic effects of Sophoridine with cisplatin on gastric cancer cells were further investigated in in vitro functional studies.RESULTS:
Sophoridine exhibited potent tumor-suppressive activities in gastric cancer cells, including inhibition of proliferation, colony formulation, migration and invasion, as well as induction of apoptosis. In addition, we further showed that Sophoridine induced G2/M cell cycle arrest via inhibiting double-stranded DNA breaks repair and enhanced the efficacy of cisplatin in gastric cancer cells. Molecular studies further revealed that Sophoridine promoted ß-catenin degradation by enhancing Estrogen-related receptor gamma (ESRRG) expression, but not depended on ubiquitination-proteasome pathway, either TRIM33-mediated (GSK3ß-independent) or altered GSK3ß activity, and thus exerted potent tumor-suppressive activities.CONCLUSION:
Sophoridine depends on targeting ESRRG/ß-catenin pathway to exert tumor-suppressive activities in gastric cancer cells and enhances the anti-tumor effect of cisplatin. Our study provided the promising preclinical anti-tumor evidence for the potential application of Sophoridine against gastric cancer.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinolizinas
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Neoplasias Gástricas
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Receptores de Estrogênio
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Alcaloides
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Beta Catenina
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
BMC Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2020
Tipo de documento:
Article