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Valproate modulates the activity of multidrug resistance efflux pumps, as a chemoresistance factor in gastric cancer cells.
Hosseini, Sayedeh Azimeh; Mirzaei, Seyed Abbas; Kermani, Shahriar; Yaghoobi, Hajar.
Afiliación
  • Hosseini SA; Student Research Commitee, Shahrekord University of Medical Sciences, Shahrekord, Iran.
  • Mirzaei SA; Department of Medical Biotechnology, School of Advanced Technology, Shahrekord University of Medical Sciences, Shahrekord, Iran.
  • Kermani S; Department of Medical Biotechnology, School of Advanced Technology, Shahrekord University of Medical Sciences, Shahrekord, Iran.
  • Yaghoobi H; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Mol Biol Rep ; 51(1): 427, 2024 Mar 18.
Article en En | MEDLINE | ID: mdl-38498238
ABSTRACT

BACKGROUND:

Drug resistance is one of the most critical problems in gastric cancer therapy. This study was performed to investigate the valproic acid effects on the proliferation of sensitive and resistant cell lines of human gastric cancer, and to explore the mechanism of the agent on multi drug resistance and apoptosis genes.

METHODS:

The cytotoxicity effect of valproic acid on the EPG85.257 and EPG85.257RDB cells was assessed by the MTT assay, and the IC50 concentration was evaluated. Apoptosis, genotoxicity, and drug resistance pump activity were evaluated using comet assay, Real-time PCR, and flow cytometry, respectively. Cell proliferation was assayed using a scratch test.

RESULTS:

Dose-dependent toxicity was recorded after treatment of cells with valproic acid. Valproic acid represented a significant growth inhibition on EPG85.257 cells with IC50 values of 5.84 µM and 4.78 µM after 48 h and 72 h treatment, respectively. In contrast, the drug-resistant counterpart represented 8.7 µM and 7.02 µM IC50 values after the same treatment time. Valproic acid induced PTEN, Bcl2, P53, Bax, P21, and caspase3 expression in EPG85.257 cells, whereas p21, p53, PTEN, and ABCB1 were overexpressed in EPG5.257RDB. Valproic acid hindered cell migration in both cell lines (P < 0.01). Valproate genotoxicity was significantly higher in the parent cells than in their resistant EPG85.257RDB counterparts. Valproate led to a 62% reduction in the daunorubicin efflux of the MDR1 pump activity.

CONCLUSIONS:

Valproate can affect drug resistance in gastric cancer via a unique mechanism independent of MDR1 expression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas Límite: Humans Idioma: En Revista: Mol Biol Rep Año: 2024 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas Límite: Humans Idioma: En Revista: Mol Biol Rep Año: 2024 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Países Bajos