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

• Published in: Cancer management and research 2019-01, Vol.11, p.2831-2848
• Main Authors: Tai, Yang, Zhang, Lin-Hao, Gao, Jin-Hang, Zhao, Chong, Tong, Huan, Ye, Cheng, Huang, Zhi-Yin, Liu, Rui, Tang, Cheng-Wei
• Format: Article
• Language: English
• Subjects: Analysis; Angiogenesis inhibitors; Anti-inflammatory agents; Apoptosis; Biological markers; Cancer; Cancer metastasis; Carcinoma; Celecoxib; Cell adhesion & migration; Cell cycle; COX-2 inhibitors; Cyclooxygenase-2; Hepatocellular carcinoma; Immunohistochemistry; Inflammation; Liver cancer; Metabolites; Nonsteroidal anti-inflammatory agents; Original Research; Prostaglandins; Prostaglandins E; Survival; Time; Tumors
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S183376

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. 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. 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. 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.