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Inhibition of CD73 expression or A2AR blockade reduces MRP1 expression and increases the sensitivity of cervical cancer cells to cisplatin.
Carrera-Martínez, Monserrat; Mora-García, María de L; García-Rocha, Rosario; Weiss-Steider, Benny; Montesinos-Montesinos, Juan J; Hernández-Montes, Jorge; Don-López, Christian A; Monroy-García, Alberto.
Afiliação
  • Carrera-Martínez M; Laboratorio de Inmunología y Cáncer, Unidad de Investigación Médica en Enfermedades Oncológicas, CMN SXXI, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico.
  • Mora-García ML; Programa de Posgrado en Ciencias Biológicas, UNAM, Ciudad de México, Mexico.
  • García-Rocha R; Doctorate Scholarship No. 579767 from CONACyT, Ciudad de México, Mexico.
  • Weiss-Steider B; Laboratorio de Inmunobiología, Unidad de Investigación en Diferenciación Celular y Cáncer-UMIEZ, FES-Zaragoza, UNAM, Ciudad de México, Mexico.
  • Montesinos-Montesinos JJ; Laboratorio de Inmunobiología, Unidad de Investigación en Diferenciación Celular y Cáncer-UMIEZ, FES-Zaragoza, UNAM, Ciudad de México, Mexico.
  • Hernández-Montes J; Laboratorio de Inmunobiología, Unidad de Investigación en Diferenciación Celular y Cáncer-UMIEZ, FES-Zaragoza, UNAM, Ciudad de México, Mexico.
  • Don-López CA; Laboratorio de Células Troncales Mesenquimales, Unidad de Investigación Médica en Enfermedades Oncológicas, CMN SXXI, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico.
  • Monroy-García A; Laboratorio de Inmunobiología, Unidad de Investigación en Diferenciación Celular y Cáncer-UMIEZ, FES-Zaragoza, UNAM, Ciudad de México, Mexico.
Cell Biochem Funct ; 41(3): 321-330, 2023 Apr.
Article em En | MEDLINE | ID: mdl-36846868
Recently, a link between the biological activity of CD73 in solid tumors and multidrug resistance protein (MRP) has been proposed. Cisplatin (CP) is the most widely used anticancer agent to treat advanced and recurrent cervical cancer (CC). However, multidrug resistance protein-1 (MRP1) is overexpressed in approximately 85% of these tumors and has been strongly associated with cisplatin resistance (CPR). In this study, we examine the involvement of CD73 and the interaction of adenosine (ADO) with its receptors (ARs) in MRP1 expression in CC cells. We found that ADO positively modulates MRP1 expression in CC cells in a dose-dependent manner. The inhibition of CD73 expression with a CD73-targeted siRNA and A2AR blockade with the selective antagonist ZM241385 significantly decreased MRP1 expression and the extrusive capacity of CC cells, making them significantly more sensitive to CP treatment than cancer cells treated with MK-751, a specific MRP1 inhibitor. These results suggest CD73 inhibition or blocking ADO signaling through A2AR could be strategies to reverse CPR in patients with advanced or recurrent CC, which is characterized by very low response rates to CP (10%-20%).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias do Colo do Útero Tipo de estudo: Diagnostic_studies Limite: Female / Humans Idioma: En Revista: Cell Biochem Funct Ano de publicação: 2023 Tipo de documento: Article País de afiliação: México País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias do Colo do Útero Tipo de estudo: Diagnostic_studies Limite: Female / Humans Idioma: En Revista: Cell Biochem Funct Ano de publicação: 2023 Tipo de documento: Article País de afiliação: México País de publicação: Reino Unido