Valproic acid induces NET cell growth arrest and enhances tumor suppression of the receptor-targeted peptide-drug conjugate via activating somatostatin receptor type II.
J Drug Target
; 24(2): 169-77, 2016.
Article
em En
| MEDLINE
| ID: mdl-26211366
ABSTRACT
BACKGROUND:
Human pancreatic carcinoids, a type of neuroendocrine tumors, are asymptomatic and difficult to diagnose, with the effects of traditional anti-cancer therapies being limited. The histone deacetylase (HDAC) inhibitor valproic acid (VPA) was evaluated for its effects alone and in combination with receptor-targeting peptide-drug conjugate via increasing drug internalization. MATERIALS ANDMETHODS:
The in vitro and in vivo assays were used to evaluate the effects of VPA and somatostatin receptor-targeting camptothecin-somatostatin conjugate (CPT-SST).RESULTS:
VPA induced proliferation suppression, cell apoptosis and cell cycle arrest. VPA acts as a HDAC inhibitor to induce a decrease of HDAC4 and an increase of acetylated histone 4 (AcH4). Meanwhile, most importantly, besides activating Notch signaling, VPA was observed to stimulate the expression of somatostatin receptor type 2 (SSTR2) that has been applied for receptor-targeting therapies. This characteristic was used for a combination therapy of VPA and CPT-SST. The combination displayed much more potent anti-tumor effects on carcinoid tumor growth by increasing SSTR2 density and drug internalization in target tumor cells.CONCLUSION:
The combination of VPA and a SSTR2-targeting agent provides us a promising approach in treatment of carcinoid tumors.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Ácido Valproico
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Receptores de Somatostatina
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Receptores de Peptídeos
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Proliferação de Células
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article