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XPA, XPC, and XPD modulate sensitivity in gastric cisplatin resistance cancer cells

Author
Pajuelo-Lozano, Natalia; Bargiela-Iparraguirre, Jone; Domínguez, Gemma; Quiroga, Adoración G.; Perona, Rosario; Sánchez-Pérez, Isabel
Entity
UAM. Departamento de Bioquímica; UAM. Departamento de Medicina; UAM. Departamento de Química Inorgánica; Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
Publisher
Frontiers Media S.A.
Date
2018-10-17
Citation
10.3389/fphar.2018.01197
Frontiers in Pharmacology 9.OCT. (2018): 1197
 
 
 
ISSN
1663-9812
DOI
10.3389/fphar.2018.01197
Funded by
This work was supported by PI1401495 and P17-01401 (supported by FEDER funds) from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain and by CTQ2015- 68779R. JB-I was supported by a fellowship from Catedra Isaac Costero, funded by Banco Santander-UAM and Beca Nacional de Posgrado CONACYT. NP-L was supported by a fellowship Programa de Formación de Profesorado Universitario REF: FPU15/04669, Ministerio de Educación, Cultura y Deporte
Project
Gobierno de España. PI1401495; Gobierno de España. P17-01401; Gobierno de España. CTQ2015- 68779R.
Editor's Version
https://doi.org/10.3389/fphar.2018.01197
Subjects
Apoptosis; Bcl-2 family; Cisplatin; Gastric cancer; NER repair; Medicina
URI
http://hdl.handle.net/10486/686117
Rights
Copyright © 2018 Pajuelo-Lozano, Bargiela-Iparraguirre, Dominguez, Quiroga, Perona and Sanchez-Perez.

Licencia Creative Commons
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.

Abstract

Cisplatin is an election drug widely used in clinic for the treatment of advanced gastric cancer. However, the heterogeneity of the gastric tumors and its resistance to the drugs, make in some cases the response very low and the prognosis unpredictable. In this manuscript we aim to find the molecular processes involved in cisplatin-induced apoptosis in two gastric cancer cell lines with different sensitivity to the treatment: AGS and MKN45. The apoptosis induction is higher in MKN45 than in AGS cells in response to CDDP. The intrinsic apoptotic pathway study revealed that MKN45 cells undergo degradation of Mcl-1 together with an increase of Bid and Bad levels, which results in sensitivity to CDDP. In addition, DNA repair NER pathway is impair in MKN45 cells due to low levels of XPC and the absence of translocation of XPA and XPD to the nucleus after stimuli. Altogether, these results suggest that NER and Bcl-2 protein family proteins are potential targets to improve the response to cisplatin treatment
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Google™ Scholar:Pajuelo-Lozano, Natalia - Bargiela-Iparraguirre, Jone - Domínguez, Gemma - Quiroga, Adoración G. - Perona, Rosario - Sánchez-Pérez, Isabel

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  • Producción científica en acceso abierto de la UAM [15094]

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