Inhibition of COX-2 with NS-398 decreases colon cancer cell motility through blocking epidermal growth factor receptor transactivation: possibilities for combination therapy.
Collectively, these observations suggest that AR is an obligatory mediator of growth factor-induced up-regulation of COX-2, PGE(2), and growth of Caco-2 cells, indicating that inhibition of AR may be a novel therapeutic approach in preventing the progression of colon cancer.
It is suggested that there is a positive feedback loop between COX-2 and PGE2, in which function of COX-2 induces generation of PGE2, and upregulation of PGE2 increases the expression of COX-2 in colon cancer.
The notion of COX-2/PGE(2) activation against GOS-induced apoptosis in colon carcinoma cells was demonstrated, and the combination of GOS and COX-2 inhibitors to treat colon carcinoma possesses clinical potential worthy of further investigation.
Our results suggest that the COX-2Val511Ala SNP does not antagonize the effect of NSAIDs on colon cancer risk and provides support that NSAID use and the COX-2Val511Ala SNP may contribute to a reduced risk of colon cancer among African Americans.
Our data further support the model in which colon cancer growth is favored when intracellular arachidonic acid levels are suppressed by inhibition of cPLA(2) or by a high-COX-2/low-cPLA(2) phenotype.
Different polysaccharide-rich extracts showed the ability to inhibit pro-inflammatory enzymes (COX-1, COX-2, hyaluronidase), a radical scavenging effect (against DPPH<sup>•</sup> and ABTS<sup>•+</sup>), and antiproliferative activity (in the A549 lung and SW480 colon cancer cell lines) in in vitro assays.
Preclinical and clinical studies suggest that 5-lipoxygenase (5-LOX), such as COX-2, is a potential target for colon cancer inhibition and, in part, contributes to cardiovascular side effects associated with COX-2 inhibitors.
The expression of cyclo-oxygenase-2 (COX-2) in the colon- cancer cells (Lovo) transfected by inducible vector for VP1u was determined by western-blot analysis.
We conclude that the loss of APC function favors the silencing of FXR expression through CpG hypermethylation in mouse colonic mucosa and human colon cells, leading to reduced expression of downstream targets (SHP, IBABP) involved in BA homeostasis while increasing the expression of factors (COX-2, c-MYC) that contribute to inflammation and colon cancer.
We aimed to address the hypothesis that platelets contribute to aberrant COX-2 expression in HT29 colon carcinoma cells and to reveal the role of platelet-induced COX-2 on the expression of proteins involved in malignancy and marker genes of epithelial-mesenchymal transition (EMT).
The activation of the COX-2/PGE<sub>2</sub> system and COX-2-dependent suppressive events were also observed in ex vivo human breast and colon cancer explant cultures and were similarly counteracted by celecoxib.
Recent research has demonstrated that colon cancer cell proliferation can be suppressed in the cells that overexpress COX-2 via generating 8-hydroxyoctanoic acid (a free radical byproduct) during dihomo-γ-linolenic acid (DGLA, an ω-6 fatty acid) peroxidation from knocking down cellular delta-5-desaturase (D5D, the key enzyme for converting DGLA to the downstream ω-6, arachidonic acid).
To further examine the COX-inhibition-independent effects of indomethacin on colorectal cancer, we used human colon cancer LS174T cells, known to have express little COX-2 and have no detectable PGE(2) production.