Relevance of transportome among the mechanisms of chemoresistance in hepatoblastoma

[EN]Approximately 20 % of hepatoblastomas (HBs) exhibit a poor response to conventional chemotherapy due to mechanisms of chemoresistance (MOCs), such as reduced intracellular drug accumulation. This study evaluated the role of transportome in the multidrug resistance (MDR) of HB. Paired HB and adja...

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Detalles Bibliográficos
Autores: Cives Losada, Candela, Asensio Martín, Maitane, Briz Sánchez, Oscar, Chinchilla Tábora, Luís Miguel, Barranco, María Manuela, Río-Álvarez, Álvaro Del, Martinez-Chantar, Maria Luz, Avila, Matias A, Cairo, Stefano, Armengol, Carolina, García Marín, José Juan, Rodríguez Macías, Rocío Isabel, Río-Álvarez, Álvaro del, Avila, Matias A., Marin, Jose J.G., Macias, Rocio I.R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/170047
Acceso en línea:http://hdl.handle.net/10366/170047
Access Level:acceso abierto
Palabra clave:Multidrug resistance
Pediatric liver cancer
Prognosis
Resistome
Sensitization
Tumor heterogeneity
Cisplatin
Hepatoblastoma
Liver Neoplasms
Drug Resistance
Cell Survival
Doxorubicin
Humans
Hep G2 Cells
Cell Line
Antineoplastic Agents
farmacologia
hepatoblastoma
neoplasias hepáticas
humanos
células Hep G2
antineoplásicos
cisplatino
resistencia a medicamentos
doxorrubicina
línea celular
supervivencia celular
Descripción
Sumario:[EN]Approximately 20 % of hepatoblastomas (HBs) exhibit a poor response to conventional chemotherapy due to mechanisms of chemoresistance (MOCs), such as reduced intracellular drug accumulation. This study evaluated the role of transportome in the multidrug resistance (MDR) of HB. Paired HB and adjacent liver tissue samples (n = 19) and HB-derived cell lines (HepG2, HuH6) were analyzed for their resistome characterization at mRNA (RT-qPCR, Taqman Low-Density Array, sequencing) and protein (western blot, immunohistochemistry, immunofluorescence) levels. Cell viability (MTT test) proliferation and migration (holographic microscopy) were determined. The impact of short-term (72 h) and long-term (>10 months) exposure of HB cells to cisplatin or doxorubicin on the transportome was investigated. Solute carrier (SLC) family of transporters showed minor relevance in HB MDR, while drug export pumps, particularly MRP2, were associated with poor response to chemotherapy. Exposure of HB cells to doxorubicin or cisplatin up-regulated MDR1, MRP1 and MRP2. In cells with induced persistent chemoresistance, the expression of genes involved in other MOCs, and epigenetic machinery was altered. Chemoresistant cells showed cross-resistance to several anticancer drugs but maintained sensitivity to cabozantinib. In conclusion, drug export pumps, but not SLC uptake transporters, are key contributors to HB chemoresistance. Cabozantinib emerges as a potential therapeutic option for HBs resistant to conventional chemotherapy.

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