Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling.
Gynecol Oncol
; 138(3): 668-75, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-26135947
ABSTRACT
OBJECTIVES:
Obesity and diabetes are well-known risk factors for the development of endometrial cancer. A high rate of aerobic glycolysis represents a key mechanism by which endometrial cancer cells consume glucose as its primary energy source. The up-regulated glycolytic pathway is a common therapeutic target whose inhibition has implications for anti-tumor activity in cancer cells. This study aimed to investigate the effect of various concentrations of glucose on cell proliferation in endometrial cancer.METHODS:
ECC-1 and Ishikawa cells were treated with low glucose (1mM), normal glucose (5mM) and high glucose (25mM), and cytotoxicity, apoptosis, cell cycle, adhesion/invasion, and changes of AMPK/mTOR/S6 and MAPK pathways were evaluated.RESULTS:
Our results revealed that high glucose increased cell growth and clonogenicity in two endometrial cancer cell lines in a dose dependent manner. Low glucose induced the activity of cleaved caspase 3 and caused cell cycle G1 arrest. High glucose increased the ability of adhesion and invasion by decreasing E-cadherin and increasing Snail expression. In addition, high glucose increased glucose uptake and glycolytic activity through modulating the AMPK/mTOR/S6 and MAPK pathways.CONCLUSIONS:
Our findings suggest that glucose stimulated cell proliferation through multiple complex signaling pathways. Targeting glucose metabolism may be a promising therapeutic strategy in the treatment of endometrial cancer.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Endométrio
/
Sistema de Sinalização das MAP Quinases
/
Proteínas Quinases Ativadas por AMP
/
Serina-Treonina Quinases TOR
/
Glucose
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Gynecol Oncol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos