<p>Suppressing growth and invasion of human hepatocellular carcinoma cells by celecoxib through inhibition of cyclooxygenase-2</p>

Abstract

Purpose: Biomarkers are lacking in hepatocellular carcinoma (HCC). Cyclooxygenase-2 (COX-2) and its metabolites play crucial roles in the process of inflammation-tumor transformation. This study was aimed to detect COX-2 expression in HCC tissues and evaluate the effects of a COX-2 inhibitor, celecoxib, on biological behaviors of HCC cell lines in vitro. Methods: COX-2 expression was detected by immunohistochemistry on a human HCC tissue microarray. The correlations of COX-2 expression with tumor clinicopathological variables and overall survival were analyzed. The proliferation, apoptosis, cell cycle distribution, invasion capacity, and related signaling molecules of HCC cells after incubated with COX-2 inhibitor celecoxib were evaluated in vitro. Results: Expression levels of COX-2 in HCC tissues were significantly higher than those in paracancerous tissues. 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. Patients with low COX-2 expression achieved better 5-year overall survival than those with high COX-2 expression. Treatment with celecoxib was sufficient to inhibit cell proliferation, promote apoptosis, and induce G0/G1 cell cycle arrest in HCC cells with concentration- and time-dependent manners. Celecoxib up-regulated E-cadherin protein through inhibiting COX-2-prostaglandin E2 (PGE2)-PGE2 receptor 2 (EP2)-p-Akt/p-ERK signaling pathway to suppress HCC cells migration and invasion. Conclusion: High COX-2 expression was associated with advanced TNM stage, larger tumor size, increased lymphovascular invasion and short survival. Targeting inhibition of COX-2 by celecoxib exhibited anti-tumor activities by suppressing proliferation, promoting apoptosis, and inhibiting the aggressive properties of HCC cells.

Metformin Synergistically Enhanced the Antitumor Activity of Celecoxib in Human Non-Small Cell Lung Cancer Cells

“…The occurrence and development of tumors is the result of tumor cell proliferation, apoptosis, and migration, which are affected by multiple conditions. The antiproliferation, proapoptosis, and antimigration effects of celecoxib have been reported in a variety of tumor cells (Jendrossek, 2013;Tai et al, 2019;Tian et al, 2019). Metformin has also been reported to slightly inhibit tumor cell growth (Cheng et al, 2019;Lee et al, 2019), which is consistent with the data in this study.…”

“…Given the possible side effects of high dose NSAIDs which may lead to the failure of clinical trials, we expected to use a lower dose of celecoxib in this research. Tai et al found that high concentrations of celecoxib from 50 μM to 70 μM can significantly cause G1 phase arrest in two liver cancer cells, Bel7402 cells and HepG2 cells ( Tai et al, 2019 ). In this study, a low dose of 25 μM celecoxib in combination with metformin significantly induced cell cycle arrest.…”

Celecoxib, a selective COX‑2 inhibitor, markedly reduced the severity of tamoxifen‑induced adenomyosis in a murine model

“…The interpretation of this finding with regard to the antiangiogenic effects of celecoxib in this model is limited. In view of the angiogenesis effect of the increased expression or activity of Cox-2, recently the inhibition of Cox-2 by celecoxib has been explored to be used in the treatment of diverse cancers such as breast cancer and hepatocellular carcinoma (18,53,54). So further should be performed in larger sample populations or in vitro to reveal the association between the inhibition of Cox-2 by celecoxib and angiogenesis, which may provide a more solid theoretical basis for the application of celecoxib for the treatment of adenomyosis.…”

Kiwi Root Extract Inhibits the Development of Endometriosis in Mice by Downregulating Inflammatory Factors

“…It has been reported that the inflammatory environment of ectopic tissue is the first step in the development of ectopic tissue and that its upstream factor IL-1 β [ 30 ] can control the expression of COX-2. Moreover, COX-2 and its metabolites have a crucial role in inflammation-tumor transformation [ 31 ]. Our study prompts that the kiwi root extract may reduce the COX-2 expression by downregulating IL-1 β , which is a key inflammatory factor, resulting in a decrease of mPGEs and PGE 2 .…”