Article
Broad Transcriptomic Impact of Sorafenib and Its Relation to the Antitumoral Properties in Liver Cancer Cells
Author/s | Contreras Bernal, Laura
Rodríguez Gil, Alfonso Muntané Relat, Jordi Cruz Díaz, Jesús de la |
Department | Universidad de Sevilla. Departamento de Genética Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Publication Date | 2022 |
Deposit Date | 2022-03-04 |
Published in |
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Awards | Premio Mensual Publicación Científica Destacada de la US. Facultad de Biología |
Abstract | Hepatocellular carcinoma (HCC) is one of the most frequent and essentially incurable cancers in its advanced stages. The tyrosine kinase inhibitor Sorafenib (Sfb) remains the globally accepted treatment for advanced HCC. ... Hepatocellular carcinoma (HCC) is one of the most frequent and essentially incurable cancers in its advanced stages. The tyrosine kinase inhibitor Sorafenib (Sfb) remains the globally accepted treatment for advanced HCC. However, the extent of its therapeutic benefit is limited. Sfb exerts antitumor activity through its cytotoxic, anti-proliferative and pro-apoptotic roles in HCC cells. To better understand the molecular mechanisms underlying these effects, we used RNA sequencing to generate comprehensive transcriptome profiles of HepG2 and SNU423, hepatoblastoma-(HB) and HCC-derived cell lines, respectively, following a Sfb treatment at a pharmacological dose. This resulted in similar alterations of gene expression in both cell lines. Genes functionally related to membrane trafficking, stress-responsible and unfolded protein responses, circadian clock and activation of apoptosis were predominantly upregulated, while genes involved in cell growth and cycle, DNA replication and repair, ribosome biogenesis, translation initiation and proteostasis were downregulated. Our results suggest that Sfb causes primary effects on cellular stress that lead to upregulation of selective responses to compensate for its negative effect and restore homeostasis. No significant differences were found specifically affecting each cell line, indicating the robustness of the Sfb mechanism of action despite the heterogeneity of liver cancer. We discuss our results on terms of providing rationalization for possible strategies to improve Sfb clinical outcomes. |
Funding agencies | Instituto de Salud Carlos III PI19/01266 Centro de Investigación Biomédica en Red Cáncer (CIBERONC) CB16/12/00480 |
Project ID. | 10.13039/501100011033
PI19/01266 PIP-0215-2020 PI-0216-2020 CB16/12/00480 US-1380874 |
Citation | Contreras Bernal, L., Rodríguez Gil, A., Muntané Relat, J. y Cruz Díaz, J.d.l. (2022). Broad Transcriptomic Impact of Sorafenib and Its Relation to the Antitumoral Properties in Liver Cancer Cells. Cancers, 14 (5), 1204. |
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