Pub. Date : 2018 Jul 1
PMID : 29514844
7 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | COX-2/PGE2 Axis Regulates HIF2alpha Activity to Promote Hepatocellular Carcinoma Hypoxic Response and Reduce the Sensitivity of Sorafenib Treatment. | Sorafenib | mitochondrially encoded cytochrome c oxidase II | Homo sapiens |
| 2 | We sought to determine whether the COX-2/PGE2 axis is involved in the regulatory mechanisms of HIF2alpha activity and of sorafenib resistance in hypoxic HCC cells.Experimental Design: The cell viability, migration, and invasion abilities were measured to analyze the effects of HIF2alpha on hypoxic HCC cells. | Sorafenib | mitochondrially encoded cytochrome c oxidase II | Homo sapiens |
| 3 | Both in vitro and in vivo HCC models were used to determine whether the COX-2/PGE2 axis is a driver of HIF2alpha level and activity, which then reduces the sensitivity of sorafenib treatment in hypoxic HCC cells.Results: Under hypoxic conditions, the COX-2/PGE2 axis effectively stabilized HIF2alpha and increased its level and activity via decreasing von Hippel-Lindau protein (p-VHL) level, and also enhanced HIF2alpha activity by promoting HIF2alpha nuclear translocation via MAPK pathway. | Sorafenib | mitochondrially encoded cytochrome c oxidase II | Homo sapiens |
| 4 | Both in vitro and in vivo HCC models were used to determine whether the COX-2/PGE2 axis is a driver of HIF2alpha level and activity, which then reduces the sensitivity of sorafenib treatment in hypoxic HCC cells.Results: Under hypoxic conditions, the COX-2/PGE2 axis effectively stabilized HIF2alpha and increased its level and activity via decreasing von Hippel-Lindau protein (p-VHL) level, and also enhanced HIF2alpha activity by promoting HIF2alpha nuclear translocation via MAPK pathway. | Sorafenib | mitochondrially encoded cytochrome c oxidase II | Homo sapiens |
| 5 | More importantly, COX-2-specific inhibitors synergistically enhanced the antitumor activity of sorafenib treatment.Conclusions: Our data obtained demonstrate that the COX/PGE2 axis acts as a regulator of HIF2alpha expression and activity to promote HCC development and reduce sorafenib sensitivity by constitutively activating the TGFalpha/EGFR pathway. | Sorafenib | mitochondrially encoded cytochrome c oxidase II | Homo sapiens |
| 6 | More importantly, COX-2-specific inhibitors synergistically enhanced the antitumor activity of sorafenib treatment.Conclusions: Our data obtained demonstrate that the COX/PGE2 axis acts as a regulator of HIF2alpha expression and activity to promote HCC development and reduce sorafenib sensitivity by constitutively activating the TGFalpha/EGFR pathway. | Sorafenib | mitochondrially encoded cytochrome c oxidase II | Homo sapiens |
| 7 | This study highlights the potential of COX-2-specific inhibitors for HCC treatment and particularly for enhancing the response to sorafenib treatment. | Sorafenib | mitochondrially encoded cytochrome c oxidase II | Homo sapiens |