RT Journal Article
T1 Broad Transcriptomic Impact of Sorafenib and Its Relation to the Antitumoral Properties in Liver Cancer Cells.
A1 Contreras, Laura
A1 Rodriguez-Gil, Alfonso
A1 Muntane, Jordi
A1 de-la-Cruz, Jesus
K1 RNA synthesis
K1 RNA-Seq
K1 Sorafenib
K1 gene ontology
K1 hepatocellular carcinoma cell line
AB 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.
PB MDPI AG
SN 2072-6694
YR 2022
FD 2022-02-25
LK http://hdl.handle.net/10668/20877
UL http://hdl.handle.net/10668/20877
LA en
NO Contreras L, Rodríguez-Gil A, Muntané J, de la Cruz J. Broad Transcriptomic Impact of Sorafenib and Its Relation to the Antitumoral Properties in Liver Cancer Cells. Cancers (Basel). 2022 Feb 25;14(5):1204.
DS RISalud
RD Apr 7, 2025