Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA337958 | ENA |
REPOSITORIES: ENA
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Project description:Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (CelebrexM-BM-.) is a selective cyclooxygenase-2 (COX-2) inhibitor wich exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of combination, we investigated the expression profile of the combination-treated liver cancer cell lines, using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes, functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell line displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semiquantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomics analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies. To identify new potential mechanisms of combined action of celecoxib and sorafenib, their effects on global gene expression in both cell lines were investigated and compared using the DNA microarray technology. Agilent 44K Human Whole Genome Oligonucleotide Microarrays (containing ~44,000 genes) were used to identify global gene expression changes in the HepG2 and Huh7 hepatocellular carcinoma (HCC) cell lines, following simultaneous treatment with 50 M-BM-5M celecoxib and 7.5 M-BM-5M sorafenib for 48 hours. All microarray experiments (a total of four) were performed in duplicates applying dye-swaps to avoid labeling bias.
2013-03-21 | E-GEOD-45340 | biostudies-arrayexpress
Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of lncRNAs expression profile in sorafenib resistant hepatocellular carcinoma cells. We identified 1240 differentially expressed lncRNAs with 576 up-regulated and 664 down-regulated (fold change > 2, P < 0.05) in sorafenib-resistant (HUH7-S) HCC cells (fold change > 2, P < 0.05) in sorafenib-resistant (HepG2-S) HCC cells, compared to parental sorafenib-sensitive (HUH7, HepG2) HCC cells by high-throughput sequencing. In addition, based on GO (Gene Ontology) term enrichment analysis, these differentially expressed lncRNAs are mainly related to binding and catalytic activity and biological regulation of metabolic processes in both the Huh7-S and HepG2-S cell lines compared to parental cell lines. Moreover, the differentially expressed genes analyzed by KEGG (Kyoto Encyclopedia of Genes and Genomes) Pathway were significantly related to tight junction. Among them, TCONS_00284048 and TCONS_00006019 expression were consistently up-regulated in resistant HCC cells, whereas both of them knock down increased the sensitivity of Huh7-S and HepG2-S cells to sorafenib.
2020-02-02 | GSE140202 | GEO
Project description:Sorafenib leads to a survival benefit in patients with advanced hepatocellular carcinoma but its use is hampered by the occurrence of drug resistance. To investigate the molecular mechanisms involved we developed five resistant human liver cell lines in which we studied morphology, gene expression and invasive potential. The cells changed their appearance, lost E-cadherin and KRT19 and showed high expression of vimentin, indicating epithelial-to-mesenchymal transition. Resistant cells showed reduced adherent growth, became more invasive and lost liver-specific gene expression. Furthermore, following withdrawal of sorafenib, the resistant cells showed rebound growth, a phenomenon also found in patients. This cell model was further used to investigate strategies for restoration of sensitivity to sorafenib. We determined gene expression profiles for 13 samples, grown in 1x106 in 25 cm² tissue flasks. Three flasks contained control samples: HepG2 cells at 20% O2/ 5% CO2/ 75% N2, not exposed to sorafenib. Four flasks contained samples from condition 1: HepG2S1 cells at 20% O2/ 5% CO2/ 75% N2, exposed to sorafenib. Three flasks contained samples from condition 2: HepG2S1 cells at 20% O2/ 5% CO2/ 75% N2, withdrawn from sorafenib. Three flasks contained samples from condition 3: HepG2S1 cells at 2% O2/ 5% CO2/ 93% N2, exposed to sorafenib.
2016-03-14 | E-GEOD-62813 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is one of the most common causes of death worldwide and the fourth most prevalent type of cancer. Whereas curative treatments such as liver transplantation, ablation or surgery are optimal for early stages, only paliative treatments are given to intermediate and advanced stages of the disease. Sorafenib is still a suitable therapeutic option for patients in whom immunotherapy is not feasible. To gain information about therapy response, we sequenced HepG2 cells treated with Sorafenib 10 µM (24 hours)
2023-12-01 | GSE225537 | GEO
Project description:Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. Like in many cancers, tumor heterogeneity in HCC hampers the development of personalized therapies. Integrative genomics contributed to characterize HCC subtypes by identifying specific genetic alterations and molecular signatures, leading to targeted drug candidates. However, no consensus was achieved for genes and pathways recurrently altered in HCC. Here, a meta-analysis of 15 independent HCC datasets identifies a comprehensive signature consisting of 935 genes commonly deregulated in HCC as compared to the surrounding non-tumor tissue (P<0.01). The 935-gene HCC signature covers well-established cancer hallmarks (e.g. proliferation, metabolic reprogramming, microenvironment remodeling) together with specific hallmarks associated with protein turnover and epigenetics. Accordingly, the 935-gene HCC signature highlights relevant drugs for systemic therapies, including including two histone deacetylase (HDAC) inhibitors (trichostatin A and vorinostat), PI3K inhibitor LY294002, mTOR inhibitor sirolimus (also known as rapamycin), alpha-estradiol and resveratrol. The impact of these drugs as compared to sorafenib that is currently used for the treatment of advanced HCC was evaluated on the viability of 6 HCC-derived cell lines. We concluded that combined therapies targeting common and subtype-specific cancer networks may represent a relevant strategy to efficiently treat liver cancer.
2016-11-15 | GSE79246 | GEO
Project description:Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. Like in many cancers, tumor heterogeneity in HCC hampers the development of personalized therapies. Integrative genomics contributed to characterize HCC subtypes by identifying specific genetic alterations and molecular signatures, leading to targeted drug candidates. However, no consensus was achieved for genes and pathways recurrently altered in HCC. Here, a meta-analysis of 15 independent HCC datasets identifies a comprehensive signature consisting of 935 genes commonly deregulated in HCC as compared to the surrounding non-tumor tissue (P<0.01). The 935-gene HCC signature covers well-established cancer hallmarks (e.g. proliferation, metabolic reprogramming, microenvironment remodeling) together with specific hallmarks associated with protein turnover and epigenetics. Accordingly, the 935-gene HCC signature highlights relevant drugs for systemic therapies, including including two histone deacetylase (HDAC) inhibitors (trichostatin A and vorinostat), PI3K inhibitor LY294002, mTOR inhibitor sirolimus (also known as rapamycin), alpha-estradiol and resveratrol. The impact of these drugs as compared to sorafenib that is currently used for the treatment of advanced HCC was evaluated on the viability of 6 HCC-derived cell lines. We concluded that combined therapies targeting common and subtype-specific cancer networks may represent a relevant strategy to efficiently treat liver cancer.
2016-11-15 | GSE85257 | GEO
Project description:Tumor cells were microdissected from FFPE sections of hepatocellular carcinoma (HCC) samples. micro RNA expression were correlated to clinical outcome and sorafenib-therapy. miRNA was labeled with the Affymetrix FlashTag Biotin HSR RNA Labeling Kit 20 microdissected hepatocellular carcinoma samples with detailed clinical data
2014-07-29 | E-GEOD-56059 | biostudies-arrayexpress
Project description:The multi-kinase inhibitor drug sorafenib is used as first line treatment for hepatocellular carcinoma and advanced renal cell carcinoma. Sorafenib mainly undergos cytochrome P450 (CYP) 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT) 1A9-mediated glucuronidation in liver, but the biotransformation of sorafenib in kidney remains unclear. Therefore, we integrated the mRNA expression data of 36 kidney samples and the corresponding metabolic activities for sorafenib to study the metabolic mechanism of sorafenib in kidney.
2018-01-03 | GSE93069 | GEO
Project description:To investigate the specific roles of SIRT1 in the development of hepatocellular carcinoma, we employed large-scale gene expression analysis to identify the molecular signature that may affect enabling characteristics of cancer cells. Differentially expressed genes were analyzed on the SNU-182 cells transfected with SIRT1 siRNA and recapitulated molecular signatures that related to hallmarks of cancer. SIRT1 expression in hepatocellular carcinoma was analyzed by RT-PCR and western blot. RNA interference-mediated protein knockdown method was used to investigate oncogenic potential of SIRT1 in hepatocelluar carcinoma
2012-03-01 | E-GEOD-32066 | biostudies-arrayexpress
Project description:In our experiments with a xenograft model, mouse-IFN (mIFN) treatment was suggested to exaggerate the antitumor effects of sorafenib on hepatocellular carcinoma in vivo. We explored how mIFN enhances the in vivo antitumor effects of sorafenib.
2017-11-01 | GSE102863 | GEO