Cancer Management and Research (Apr 2019)

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

  • Tai Y,
  • Zhang LH,
  • Gao JH,
  • Zhao C,
  • Tong H,
  • Ye C,
  • Huang ZY,
  • Liu R,
  • Tang CW

Journal volume & issue
Vol. Volume 11
pp. 2831 – 2848

Abstract

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Yang Tai,1,* Lin-Hao Zhang,1,* Jin-Hang Gao,1,2 Chong Zhao,2 Huan Tong,1 Cheng Ye,1 Zhi-Yin Huang,1 Rui Liu,2 Cheng-Wei Tang1,21Laboratory of Gastroenterology & Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People’s Republic of China; 2Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People’s Republic of China *These authors contributed equally to this workPurpose: 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.Keywords: cyclooxygenase-2, hepatocellular carcinoma, celecoxib, survival

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