In addition, it was confirmed that the anticancer efficacy of avicularin in HCC was dependent on the regulation of NF‑κB (p65), COX‑2 and PPAR‑γ activities.
Previous studies have demonstrated that the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib shows efficacy against multiple cancers, including hepatocellular carcinoma.
The co-expression of iNOS with COX-2 may portend a particularly aggressive cancer phenotype in HCC and at the same time reveal an opportunity for pharmacological intervention.
Western blot results showed that the knockdown of PSMD4 blocked the expression of cyclooxygenase 2 (COX2), phosphorylated Sarcoma tyrosine kinase (P-SRC) and Bcl-2, but improved the levels of p53 and Bax in HCC, lung cancer, colorectal cancer, breast cancer and endometrial cancer cell lines.
Mechanistic studies revealed that MBL could interact directly with HSCs and inhibit HCC-induced HSCs activation <i>via</i> downregulating the extracellular signal-regulated kinase (ERK)/COX-2/PGE<sub>2</sub> signaling pathway.
This effect was reversed by myristoylated AKT, a constitutively active form of AKT, suggesting an involvement of CDHR2-AKT-COX2 axis in the suppression of HCC growth.
Our study reveals that ketoconazole, a broad-spectrum antifungal agent, activates PINK1/Parkin-mediated mitophagy by downregulating COX-2, consequently resulting in the acceleration of apoptosis and thereby inhibiting the growth of HCC.
The dysregulation of signaling pathways such as transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), Wnt/β-catenin (WNT), cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor α (PPARα) by HCV core protein is implicated in the development of HCC.
In conclusion, the findings of the present study provide evidence that the STAT3-COX-2 signaling pathway is involved in NaHS-induced cell proliferation, migration, angiogenesis and anti-apoptosis in PLC/PRF/5 cells, and suggest that the positive feedback between STAT3 and COX-2 may serve a crucial role in hepatocellular carcinoma carcinogenesis.
In a further study, we showed that inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the growth of HCC cells and tumor formation than either of them alone, suggesting that dual governing of YAP and COX-2 may lead to the discovery of promising therapeutic strategies for HCC patients via blocking this positive feedback loop.
More importantly, COX-2-specific inhibitors synergistically enhanced the antitumor activity of sorafenib treatment.<b>Conclusions:</b> Our data obtained demonstrate that the COX/PGE2 axis acts as a regulator of HIF2α expression and activity to promote HCC development and reduce sorafenib sensitivity by constitutively activating the TGFα/EGFR pathway.
Previous researches indicated that cyclooxygenase-2 (Cox-2) might be involved in P-glycoprotein (P-gp)-mediated multidrug resistance in hepatocellular carcinoma cells.
Parameters under investigation included hepatic, non-hepatic enzymes, oxidative stress, pro-inflammatory cytokines, COX-2 and NF-κB level along with histopathological examination in HCC rats.
Using cell-based experiments, we revealed that DENV-2 infection significantly induced COX-2 expression and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) production in human hepatoma Huh-7 cells.