COX-2 level is significantly lower in nevi than in melanomas, increases gradually with progression of these malignant cancers and reaches the highest values in metastases.
In addition, GR agonist treatment or miR-708 mimic transfection remarkably inhibited IKKβ expression and suppressed nuclear factor-kappaB (NF-κB) activity and its downstream target genes, including COX-2, cMYC, cyclin D1, Matrix metalloproteinase (MMP)-2, MMP-9, CD24, CD44 and increased p21CIP1 and p27KIP1 that are known to be involved in proliferation, cell-cycle progression, metastasis and CSC marker protein.
Celecoxib (CXB), a selective cyclooxygenase-2 (COX-2) inhibitor, has antiangiogenetic activity and inhibitory effect on tumor metastasis, and can also enhance the sensitivity of chemotherapeutic drug doxorubicin (DOX) in breast cancer.
It suppressed the expression of NF-κB and NF-κB-regulated gene products such as COX-2, survivin and MMP-9 which are involved in the regulation of different processes like proliferation, survival, invasion, and metastasis of OSCC cells.
Moreover, uptake of CEMIP<sup>+</sup> exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnf and Ccl/Cxcl, known to promote brain vascular remodelling and metastasis.
The cytokine-mediated upregulation of metastasis- and inflammatory-associated genes, which are downstream genes of STAT3 including the intercellular adhesion molecule-1, matrix metalloproteinase-9, inducible nitric oxide synthase, and cyclo-oxygenase 2 (COX-2), were also significantly abolished by myricetin treatment.
The TNM stage III-IV, tumor size >5 cm, lymphovascular invasion and distant metastasis was higher in high COX-2 expression group compared with that in low COX-2 expression group.
The effect of PLA2G4A downstream signaling, including Cyclooxygenase 2, Prostaglandin E2(PGE2) and Signal transducer and activator of transcription 3(STAT3), on EMT and metastasis was further detected with in vitro and in vivo experiments.
The present study aimed to investigate the mechanism by which cyclooxygenase‑2 (COX‑2) promotes the metastasis of MG‑63 osteosarcoma cells through the PI3K/AKT/NF‑κB pathway.
COX-2 expression was not correlated with age, gender, tumor location, cancer histology, or necrosis (<i>P </i>><i> </i>0.1), but was significantly associated with tumor grade (high grade vs. low grade: OR = 4.81, <i>P </i><<i> </i>0.001), clinical stage (stage 3-4 vs. stage 1-2: OR = 4.89, <i>P </i><<i> </i>0.001), and metastasis (yes vs. no: OR = 3.53, <i>P </i><<i> </i>0.001).
COX-2 induces cancer stem cell (CSC)-like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells.
However, COX-2 expression in mCTCs tended to have a higher rate in patients with metastasis compared with those without metastasis (72.0% vs 42.8%; P = 0.072).
In summary, BBR inhibited EC tumor growth and metastasis via miR-101/COX-2/PGE2 signaling pathways, suggesting the usage of BBR as a potential anticancer drug for treating EC.
Phytochemicals from whole plant foods are protective against oxidative stress, inhibit cell proliferation, induce cell-cycle arrest, and apoptosis, act as antiangiogenesis factors, and inhibit cyclooxygenase-2, which has been related to metastasis.
In addition, knock-down of COX-2 by siRNA reduced the experimental lung metastasis formation of suspension cultured BCCs, which was associated with a remarkable decrease in retention and survival of BCCs in lungs of mice in the early stage of metastasis.
It was known that alterations in COX2 gene functions contribute to the inflammation process thus induce cancer progression, including cell proliferation, apoptosis, adhesion, invasion and metastasis.
Further study suggested that AKT1 and cyclooxygenase-2 (COX2; PTGS2) might mediate the CXCR2 signaling to inversely control the breast cancer metastasis and chemoresistance through the regulation of EMT, apoptosis, and senescence.
In leukemia and lymphoma, an increased activity of COX-2 and subsequent increase in prostaglandins (PGs) concentration allow cancer cells to evade immune response and contribute to metastases.
Overexpression of COX-2 has been found in a majority of breast carcinomas, and has also been associated with increased severity and the development of the metastasis.