Meloxicam suppresses hepatocellular carcinoma cell proliferation and migration by targeting COX-2/PGE2-regulated activation of the β-catenin signaling pathway

  • Authors:
    • Tao Li
    • Jingtao Zhong
    • Xiaofeng Dong
    • Peng Xiu
    • Fuhai Wang
    • Honglong Wei
    • Xin Wang
    • Zongzhen Xu
    • Feng Liu
    • Xueying Sun
    • Jie Li
  • View Affiliations

  • Published online on: April 20, 2016     https://doi.org/10.3892/or.2016.4764
  • Pages: 3614-3622
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Abstract

Recurrence and metastasis are the two leading causes of poor prognosis of hepatocellular carcinoma (HCC) patients. Cyclooxygenase (COX)-2 is overexpressed in many types of cancers including HCC and promotes its metastasis. Meloxicam is a selective COX-2 inhibitor that has been reported to exert an anti-proliferation and invasion/migration response in various tumors. In this study, we examined the role of meloxicam on HCC cell proliferation and migration and explored the molecular mechanisms underlying this effect. We found that meloxicam inhibited HCC cell proliferation and had a cell cycle arrest effect in human HCC cells. Furthermore, meloxicam suppressed the ability of HCC cells expressing higher levels of COX-2 and prostaglandin E2 (PGE2) to migration via potentiating expression of E-cadherin and alleviating expression of matrix metalloproteinase (MMP)-2 and -9. COX-2/PGE2 has been considered to activate the β-catenin signaling pathway which promotes cancer cell migration. We found that treatment with PGE2 significantly enhanced nuclear accumulation of β-catenin and the activation of GSK3β which could be reversed by meloxicam in HCC cells. We also observed that HCC cell migration and upregulation of the level of MMP-2/9 and downregulation of E-cadherin induced by PGE2 were suppressed by FH535, an inhibitor of β-catenin. Taken together, these findings provide a new treatment strategy against HCC proliferation and migration.
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June-2016
Volume 35 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Li T, Zhong J, Dong X, Xiu P, Wang F, Wei H, Wang X, Xu Z, Liu F, Sun X, Sun X, et al: Meloxicam suppresses hepatocellular carcinoma cell proliferation and migration by targeting COX-2/PGE2-regulated activation of the β-catenin signaling pathway. Oncol Rep 35: 3614-3622, 2016.
APA
Li, T., Zhong, J., Dong, X., Xiu, P., Wang, F., Wei, H. ... Li, J. (2016). Meloxicam suppresses hepatocellular carcinoma cell proliferation and migration by targeting COX-2/PGE2-regulated activation of the β-catenin signaling pathway. Oncology Reports, 35, 3614-3622. https://doi.org/10.3892/or.2016.4764
MLA
Li, T., Zhong, J., Dong, X., Xiu, P., Wang, F., Wei, H., Wang, X., Xu, Z., Liu, F., Sun, X., Li, J."Meloxicam suppresses hepatocellular carcinoma cell proliferation and migration by targeting COX-2/PGE2-regulated activation of the β-catenin signaling pathway". Oncology Reports 35.6 (2016): 3614-3622.
Chicago
Li, T., Zhong, J., Dong, X., Xiu, P., Wang, F., Wei, H., Wang, X., Xu, Z., Liu, F., Sun, X., Li, J."Meloxicam suppresses hepatocellular carcinoma cell proliferation and migration by targeting COX-2/PGE2-regulated activation of the β-catenin signaling pathway". Oncology Reports 35, no. 6 (2016): 3614-3622. https://doi.org/10.3892/or.2016.4764