[Synergistic anti-tumor effect of obatoclax and MG-132 in esophageal cancer cell line CaES-17].
Nan Fang Yi Ke Da Xue Xue Bao
; 36(4): 506-13, 2016 Apr.
Article
em Zh
| MEDLINE
| ID: mdl-27113178
ABSTRACT
OBJECTIVE:
To explore whether MG-132 could enhance the anti-tumor activity of obatoclax against esophageal cancer cell line CaES-17.METHODS:
MTT assay was used to determine the cytotoxicity of obatoclax and MG-132 in CaES-17 cells. The IC(50) of obatoclax and MG-132 were used to determine the molar ratio (12.4) of the two drugs for combined treatment of the cells. The concentrations of obatoclax and MG-132 ranged from 1/8 IC(50) to 4 IC(50) after serial dilution, and their combination index (CI) was calculated using CompuSyn software. The expression of ubiquitin and the cleavage of PARP, caspase-9, phospho-histone H3 and phospho-aurora A/B/C in the exposed cells were examined with Western blotting; the cell apoptosis was measured by flow cytometry with Annexin V staining, and the percentage of cells in each cell cycle phase was also determined by flow cytometry.RESULTS:
The CI of obatoclax and MG-132 was 0.296 for a 50% inhibition of Caes-17 cells and was 0.104 for a 95% inhibition. The cells treated with obatoclax or MG-132 alone showed increased expression of ubiquitin and cleavage of PARP and caspase-9. Compared with the cells treated with obatoclax or MG-132 alone, the cells with a combined treatment exhibited significantly increased expression of ubiquitin, cleavage of PARP and caspase-9, and expression of phospho-Histone H3 (P<0.05). The combined treatment of the cells also resulted in significantly increased expression of phospho-Aurora A/B/C compared with obatoclax treatment alone. The cells with the combined treatment showed significantly higher percentages of apoptotic cells and cells in sub-G(1) and G(2)/M phases compared with the cells treated with either of the drugs (P<0.05).CONCLUSION:
Obatoclax combined with MG-132 shows a significant synergistic anti-tumor effect against esophageal cancer CaES-17 cells by inducing apoptosis and cell cycle arrest.
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Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Esofago
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Neoplasias Esofágicas
/
Leupeptinas
Limite:
Humans
Idioma:
Zh
Revista:
Nan Fang Yi Ke Da Xue Xue Bao
Ano de publicação:
2016
Tipo de documento:
Article