Synergistic antitumor activities of sepantronium bromide (YM155), a survivin suppressant, in combination with microtubule-targeting agents in triple-negative breast cancer cells.
Biol Pharm Bull
; 36(12): 1921-7, 2013.
Article
em En
| MEDLINE
| ID: mdl-24432379
ABSTRACT
Triple-negative breast cancer (TNBC) has a poor prognosis compared to other subtypes, and effective treatment options are limited to cytotoxic agents, including microtubule-targeting agents, due to the lack of molecular targets. Here, we examined the combined effect of sepantronium bromide (YM155) and microtubule-targeting agents in TNBC models. The combination of YM155 with docetaxel showed synergistic antiproliferative and caspase 3/7-inducing effects in MRK-nu-1 and MDA-MB-453 human TNBC cell lines in vitro. YM155 also synergistically enhanced the efficacies of other microtubule-targeting agents, including paclitaxel and vinorelbine, which induced accumulation of survivin at the G2/M phase, whereas it did not affect the efficacy of doxorubicin. Combination treatment with YM155 and microtubule-targeting agents decreased the accumulation of survivin at the G2/M phase and induced greater apoptosis than either single agent alone. Further, combination treatment with YM155 and docetaxel also had a synergistic antitumor effect, achieving complete regression without exacerbation of body weight loss in all mice, in a MRK-nu-1 human TNBC xenograft model. These results suggest that survivin inhibition synergistically sensitize human TNBC cells to microtubule-targeting agents.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Proteínas Inibidoras de Apoptose
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Neoplasias de Mama Triplo Negativas
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Biol Pharm Bull
Ano de publicação:
2013
Tipo de documento:
Article