Targeting HCCR expression resensitizes gastric cancer cells to chemotherapy via down-regulating the activation of STAT3.
Sci Rep
; 6: 24196, 2016 Apr 07.
Article
em En
| MEDLINE
| ID: mdl-27052330
ABSTRACT
The human cervical cancer oncogene (HCCR) has been found to be overexpressed in a variety of human cancers. However, the level of expression of HCCR and its biological function in gastric cancer are largely unknown. In this study, we evaluated HCCR expression in several gastric cancer cell lines and in one normal gastric mucosal cell line. We established a 5-FU-resistant gastric cancer cell subline, and we evaluated its HCCR expression. HCCR expression levels were high in gastric cancer lines, and expression was significantly increased in the 5-FU-resistant cancer cell subline. HCCR expression affected cell growth by regulating apoptosis in the cancer cells, and it had a positive correlation with p-STAT3 expression. Western blot and luciferase reporter assays showed that the activation of STAT3 upregulated HCCR expression in a positive feedback loop model. In vivo and in vitro studies showed that HCCR plays an important role in the apoptosis induced by 5-FU. Our data demonstrate that HCCR is probably involved in apoptosis and cancer growth and that it functions as a p-STAT3 stimulator in a positive feedback loop model. In gastric cancer cells, HCCR confers a more aggressive phenotype and resistance to 5-FU-based chemotherapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Regulação Neoplásica da Expressão Gênica
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Proteínas Proto-Oncogênicas
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Fator de Transcrição STAT3
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Fluoruracila
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article