Resveratrol Increases Anti-Proliferative Activity of Bestatin Through Downregulating P-Glycoprotein Expression Via Inhibiting PI3K/Akt/mTOR Pathway in K562/ADR Cells.
J Cell Biochem
; 117(5): 1233-9, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-26460589
ABSTRACT
Multidrug resistance (MDR) is a major obstacle in the clinical therapy of hematological malignancies. P-glycoprotein (P-gp) overexpression results in reduction of intracellular drug concentration with a consequence that the cytotoxicity of anti-tumor drugs is decreased, which leads to MDR in K562/ADR cells. In this study, we found that resveratrol enhanced the anti-proliferative activity of bestatin in K562/ADR cells. Co-treatment with resveratrol, IC50 values of bestatin in K562/ADR cells significantly decreased and activation of caspase-3 and caspase-8 increased, which indicated that resveratrol potentiated bestatin-induced apoptosis. Resveratrol increased the intracellular concentration of bestatin through inhibiting P-gp function and downregulating P-gp expression at mRNA and protein levels, which increased anti-proliferative activity of bestatin in K562/ADR cells. Resveratrol decreased the phosphorylation of Akt and mTOR but did not affect the phosphorylations of JNK or ERK1/2. These results demonstrated that resveratrol could increase the anti-proliferative activity of bestatin through downregulating P-gp expression via suppressing the PI3K/Akt/mTOR signaling pathway.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estilbenos
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Fosfatidilinositol 3-Quinases
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Proliferação de Células
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Proteínas Proto-Oncogênicas c-akt
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Serina-Treonina Quinases TOR
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Leucina
Limite:
Humans
Idioma:
En
Revista:
J Cell Biochem
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China