Bag-1 silencing enhanced chemotherapeutic drug-induced apoptosis in MCF-7 breast cancer cells affecting PI3K/Akt/mTOR and MAPK signaling pathways.

Kilbas, Pelin Ozfiliz; Akcay, Izzet Mehmet; Doganay, Gizem Dinler; Arisan, Elif Damla

Kilbas, Pelin Ozfiliz; Akcay, Izzet Mehmet; Doganay, Gizem Dinler; Arisan, Elif Damla.

Afiliación

Kilbas PO; Department of Molecular Biology-Genetics and Biotechnology, Istanbul Technical University, Istanbul, Turkey.
Akcay IM; Department of Molecular Biology and Genetics, Istanbul Kultur University, Istanbul, Turkey.
Doganay GD; Department of Molecular Biology-Genetics and Biotechnology, Istanbul Technical University, Istanbul, Turkey.
Arisan ED; Department of Molecular Biology-Genetics and Biotechnology, Istanbul Technical University, Istanbul, Turkey. gddoganay@itu.edu.tr.

Mol Biol Rep ; 46(1): 847-860, 2019 Feb.

Article en En | MEDLINE | ID: mdl-30661182

RESUMEN

The multifunctional anti-apoptotic Bag-1 protein has important roles in apoptosis, proteasome-mediated degradation, transcriptional regulation, and intracellular signaling. Bag-1 promotes cell survival and proliferation, and is overexpressed in breast cancer. Therefore, Bag-1-targeted therapy might be a promising strategy to treat breast cancer. However, the effects of Bag-1 silencing in combination with conventional chemotherapeutic drugs on cell viability and major signaling pathways have not yet been fully investigated in breast cancer cells. In this study, we investigated the cytotoxic effects of Bag-1 silencing, alone and in combination with cisplatin or paclitaxel treatment, in MCF-7 breast cancer cells. Bag-1 knockdown by shRNA or siRNA transfection sensitized MCF-7 cells to apoptosis induced by cisplatin or paclitaxel. Combination of Bag-1 silencing and drug treatment more potently downregulated the pro-survival PI3K/Akt/mTOR and p44/42 mitogen activated protein kinase (MAPK) pathways, and more potently upregulated the stress-activated p38 and SAPK/JNK MAPK pathways. Bag-1-silenced drug-treated cells had also highly reduced proliferative capacity, downregulated cyclin-cyclin dependent kinase complexes and upregulated tumor suppressors p21 and Rb. These results overall indicated that Bag-1 silencing enhanced cisplatin- or paclitaxel-induced cytotoxicity through multiple pathways. In conclusion, Bag-1 targeted therapy might enhance the therapeutic potential of conventional anti-cancer drugs in the treatment of breast cancer.

Asunto(s)

Antineoplásicos/farmacología; Apoptosis; Neoplasias de la Mama/metabolismo; Neoplasias de la Mama/patología; Proteínas de Unión al ADN/genética; Silenciador del Gen; Transducción de Señal/efectos de los fármacos; Factores de Transcripción/genética; Apoptosis/efectos de los fármacos; Caspasas/metabolismo; Ciclo Celular/efectos de los fármacos; Supervivencia Celular/efectos de los fármacos; Cisplatino/farmacología; Quinasas Ciclina-Dependientes/metabolismo; Regulación hacia Abajo/efectos de los fármacos; Activación Enzimática/efectos de los fármacos; Femenino; Humanos; Sistema de Señalización de MAP Quinasas/efectos de los fármacos; Células MCF-7; Paclitaxel/farmacología; Fosfatidilinositol 3-Quinasas/metabolismo; Proteínas Proto-Oncogénicas c-akt/metabolismo; Serina-Treonina Quinasas TOR/metabolismo; Regulación hacia Arriba/efectos de los fármacos

Palabras clave

Apoptosis; Bag-1 siRNA/shRNA; Breast cancer; Chemotherapeutic agents; MAPK; PI3K/Akt/mTOR pathway

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: Factores de Transcripción / Neoplasias de la Mama / Transducción de Señal / Apoptosis / Silenciador del Gen / Proteínas de Unión al ADN / Antineoplásicos Límite: Female / Humans Idioma: En Revista: Mol Biol Rep Año: 2019 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Países Bajos

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google