Cyclooxygenase-2 in cancer: A review

J Cell Physiol. 2019 May;234(5):5683-5699. doi: 10.1002/jcp.27411. Epub 2018 Oct 20.


Cyclooxygenase-2 (COX-2) is frequently expressed in many types of cancers exerting a pleiotropic and multifaceted role in genesis or promotion of carcinogenesis and cancer cell resistance to chemo- and radiotherapy. COX-2 is released by cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, and cancer cells to the tumor microenvironment (TME). COX-2 induces cancer stem cell (CSC)-like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells. COX-2 mediated hypoxia within the TME along with its positive interactions with YAP1 and antiapoptotic mediators are all in favor of cancer cell resistance to chemotherapeutic drugs. COX-2 exerts most of the functions through its metabolite prostaglandin E2. In some and limited situations, COX-2 may act as an antitumor enzyme. Multiple signals are contributed to the functions of COX-2 on cancer cells or its regulation. Members of mitogen-activated protein kinase (MAPK) family, epidermal growth factor receptor (EGFR), and nuclear factor-κβ are main upstream modulators for COX-2 in cancer cells. COX-2 also has interactions with a number of hormones within the body. Inhibition of COX-2 provides a high possibility to exert therapeutic outcomes in cancer. Administration of COX-2 inhibitors in a preoperative setting could reduce the risk of metastasis in cancer patients. COX-2 inhibition also sensitizes cancer cells to treatments like radio- and chemotherapy. Chemotherapeutic agents adversely induce COX-2 activity. Therefore, choosing an appropriate chemotherapy drugs along with adjustment of the type and does for COX-2 inhibitors based on the type of cancer would be an effective adjuvant strategy for targeting cancer.

Keywords: COX-2; NF-κβ; cancer cell; prostaglandin.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cancer-Associated Fibroblasts / drug effects
  • Cancer-Associated Fibroblasts / enzymology*
  • Cancer-Associated Fibroblasts / pathology
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Humans
  • Macrophages / drug effects
  • Macrophages / enzymology*
  • Macrophages / pathology
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / enzymology*
  • Neoplastic Stem Cells / pathology
  • Signal Transduction
  • Tumor Microenvironment


  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase 2
  • PTGS2 protein, human