Title: Combination of celecoxib and sorafenib provides synergistic antiproliferative and proapoptotic effects in human liver cancer cells
Organism(s): Homo sapiens
Description: Transcriptional profiling of HepG2 and Huh7 cells treated with celecoxib plus the kinase inhibitor sorafenib. [original 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 (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which 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 µM celecoxib and 7.5 µM sorafenib for 48 hours. All microarray experiments (a total of four) were performed in duplicates applying dye-swaps to avoid labeling bias.]
Design(s): transcription profiling by array
Experimental factor(s):
2 recorded
sorafenib control condition
2 recorded
celecoxib control condition
cell line
2 recorded
Hep-G2 cell HuH-7 cell
Publication(s): Cervello M, Bachvarov D, Lampiasi N, Cusimano A, Azzolina A, McCubrey JA, Montalto G.
Novel combination of sorafenib and celecoxib provides synergistic anti-proliferative and pro-apoptotic effects in human liver cancer cells. PubMed:23776502

Sample attribute(s):
cell line
2 recorded
Hep-G2 cell HuH-7 cell
2 recorded
Cy3 Cy5
cell type
1 recorded
hepatocellular carcinoma cell line
1 recorded
Homo sapiens
Contact(s): Dimcho BachvarovDimcho Bachvarov
Release Date: 3/21/2013
Submission Date:
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Assay Downloads
transcription profiling using DNA microarray
4 assays