Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an antitumour effect on peritoneal carcinomatosis.
Br J Cancer
; 113(3): 433-42, 2015 Jul 28.
Article
en En
| MEDLINE
| ID: mdl-26180928
ABSTRACT
BACKGROUND:
Suppressor of cytokine signaling1 (SOCS1) is a negative regulator of various cytokines. Recently, it was investigated as a therapeutic target in various cancers. However, the observed antitumour effects of SOCS1 cannot not be fully explained without taking inhibition of proliferation signalling into account. Our aim was to discover a new mechanism of antitumour effects of SOCS1 for gastric cancer (GC).METHODS:
We analysed the mechanism of antitumour effect of SOCS1 in vitro. In addition, we evaluated antitumour effect for GC using a xenograft peritoneal carcinomatosis mouse model in preclinical setting.RESULTS:
We confirmed that SOCS1 suppressed proliferation in four out of five GC cell lines. SOCS1 appeared to block proliferation by a new mechanism that involves cell cycle regulation at the G2/M checkpoint. We showed that SOCS1 influenced cell cycle-associated molecules through its interaction with ataxia telangiectasia and Rad3-related protein. The significant difference in therapeutic effects was noted in terms of the post-treatment weight and total photon count of the intra-abdominal tumours.CONCLUSION:
Forced expression of SOCS1 revealed a heretofore-unknown mechanism for regulating the cell cycle and may represent a novel therapeutic approach for the treatment of peritoneal carcinomatosis of GC.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Peritoneales
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Neoplasias Gástricas
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Carcinoma
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Terapia Genética
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Proteínas Supresoras de la Señalización de Citocinas
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Puntos de Control de la Fase G2 del Ciclo Celular
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article