COX-2 mRNA expression in gastric carcinoma tissue is correlated closely with depth of invasion, indicating that COX-2 is involved in the growth of gastric carcinoma.
Further, while COX-2 itself is known to be inducible in inflammation, COX-2 expression levels correlated well with the capabilities of these clones for not only in vitro motility and invasion but also in vivo metastasis, and COX-2 inhibitors were shown for the first time to reduce lung cancer metastasis in vivo.
Expression of Cox-2 is elevated in gastric adenocarcinomas, which correlates with several clinicopathological parameters, including depth of invasion and lymph node metastasis.
COX-2 expression is strongly correlated with increased tumor microvasculature density and plays an important role in inhibiting apoptosis, stimulating angiogenesis and promoting tumor cell metastasis and invasion.
For patients with ESCC, DDH overexpression was positively correlated with smoking habit, tumor stage, number of metastatic lymph nodes, lymphovascular invasion and COX-2 expression, and inversely correlated with GST and nm23-H1 expressions, but not related to mdr-1 or HER-2/neu expressions.
COX-2 expression was scored by the percentage of COX-2-positive neoplastic cells, and proliferative activity was assessed by the Ki-67 labeling index at the deepest area of invasion.
COX-2 also played a role in LPA-induced invasion and migration, as treatment with the COX-2 specific inhibitor NS-398 reduced LPA-induced proMMP-2 protein expression and activation and blocked MMP-dependent motility and invasive activity.
Our data demonstrate that B[a]P-induced changes in invasion are mediated through augmented COX-II expression and PGE(2) production involving an AhR regulated pathway.
We found that TNF induced the expression of gene products involved in antiapoptosis (IAP1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin), proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression.
Moreover, COX-1/COX-2 inhibitors block ET-induced PGE(2) and VEGF secretion, matrix metalloproteinase (MMP) activation, and cell invasion, indicating that both enzymes function as downstream mediators of ET-induced invasive properties.
COX-2 expression coincided with that of VEGF-C. Recombinant human VEFG-C-treated HeLa cells showed increased proliferation and invasion in a dose-depended manner while NS398, a specific inhibitor of COX-2, blocked the invasive ability of HeLa.
Treatment of cells with GA enhanced apoptosis induced by tumor necrosis factor (TNF) and chemotherapeutic agents, inhibited the expression of gene products involved in antiapoptosis (IAP1 and IAP2, Bcl-2, Bcl-x(L), and TRAF1), proliferation (cyclin D1 and c-Myc), invasion (COX-2 and MMP-9), and angiogenesis (VEGF), all of which are known to be regulated by NF-kappaB.