A bidirectional effect of Rac1 inhibition-Protects radiation-induced intestinal injury while inhibits tumor.
Life Sci
; 240: 117105, 2020 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-31786196
ABSTRACT
AIMS:
To investigate whether Rac1 inhibition can alleviate radiation-induced intestinal injury (RIII), meanwhile exist no protection on tumors. MATERIALS ANDMETHODS:
Rac1 inhibition was achieved by its specific inhibitor, NSC23766. Mice were pretreated with different intraperitoneal injections, which were normal saline for NS group (N = 9), and 2.5 mg/kg and 5 mg/kg of NSC23766 for Low-Dose group (N = 9) and High-Dose group (N = 9), respectively. After total body irritation (10Gy), small intestinal tissues were collected for Hematoxylin-Eosin (H&E) staining and Terminal-deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling (TUNEL). Intestinal epithelial and tumor cell lines, namely MODE-k and CT-26, were used to further study the role of Rac1 inhibition on radiation damage. Flow cytometry was used to detect changes in reactive oxygen species production, cell cycles and mitochondrial membrane potential, the latter was also checked by fluorescence microscope. Changes of protein-expression associated with apoptosis and cell cycles were detected by Western blotting to explain the possible molecular mechanism. KEYFINDINGS:
Height of intestine villi and depth of crypt were higher (P < 0.01) and apoptosis ratio lower (P < 0.01) in High-Dose group compared with those in NS group. After radiation, Rac1 inhibition pre-treatment improved the vitality (P < 0.01) and reduced the apoptosis (P < 0.01) in MODE-k while yielded opposite results in CT-26, and reduced ROS production of MODE-k (P < 0.01) while had little effect on that of CT-26. Rac1 inhibition differently affected the cell cycles of normal cells and that of tumor cells.SIGNIFICANCE:
Inhibition of Rac1 could alleviate RIII, meanwhile assist the killing effect of radiation on tumor cells.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
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Lesões Experimentais por Radiação
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Protetores contra Radiação
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Neuropeptídeos
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Proteínas rac1 de Ligação ao GTP
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Aminoquinolinas
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Neoplasias Intestinais
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Intestinos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article