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 (Celebrex®) 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.

2013-03-21 | GSE45340 | GEO

A Comprehensive Assessment of Apigenin as an Antiproliferative, Proapoptotic, Antiangiogenic and Immunomodulatory Phytocompound.

Project description: Not available

| S-EPMC6521017 | biostudies-literature

Regulation of transactivation-independent proapoptotic activity of p53 by FOXO3a.

Project description: Not available

| S-EPMC1482564 | biostudies-literature

p53 acetylation is crucial for its transcription-independent proapoptotic functions.

Project description: Not available

| S-EPMC2670122 | biostudies-literature

Hey1- and p53-dependent TrkC proapoptotic activity controls neuroblastoma growth.

Project description: Not available