Combined chemotherapy with cyclooxygenase-2 (COX-2) inhibitors in treating human cancers: Recent advancement

• Published in: Biomedicine & pharmacotherapy Vol. 129; p. 110389
• Main Authors: Li, Shuangshuang, Jiang, Min, Wang, Lu, Yu, Shuwen
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-09-2020; Elsevier
• Subjects: Animals; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer treatment; Chemotherapy; Combination medication; COX-2 inhibitor; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - adverse effects; Cyclooxygenase 2 Inhibitors - therapeutic use; Drug Synergism; Humans; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - pathology; Signal Transduction; Treatment Outcome; Combination medication; Chemotherapy; COX-2 inhibitor; Cancer treatment
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.110389

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•Chemotherapy is standardized treatment of cancers but with unsatisfactory efficacy.•Overexpression of COX-2 is associated with carcinogenesis and cancer progression.•COX-2 inhibitors can exert anti-tumor effects on a variety of cancers.•Such a combination is beneficial to reduce toxicity and chemoresistance and enhance sensitivity.•The review discussed the molecular mechanism of the combinations.
Chemotherapy with a single chemotherapeutic agent or a combined chemotherapeutic regimen is the clinically standardized treatment for almost all human cancers. Upregulated expression of cyclooxygenase (COX)-2, also known as prostaglandin-endoperoxide synthase (PTGS), is associated with human carcinogenesis and cancer progression and COX-2 inhibitors show antitumor activity in different human cancers. Thus, a combination of chemotherapeutic agents with COX-2 inhibitors has been shown to improve therapeutic effects on human cancers. This review discusses and summarizes recent advances in cancer control and treatment using various antineoplastic drugs combined with COX-2 inhibitors. These combinations showed synergistic antitumor effects. At the gene level, COX-2 inhibitors can reduce inflammatory factors thereby regulating macrophage recruitment for activating the antitumor immune microenvironment; downregulating vascular endothelial growth factor (VEGF) to inhibit tumor angiogenesis; and inhibiting the PI3K/Akt signaling pathway to induce tumor cell apoptosis. In addition, such a combination can reduce toxicity and chemoresistance and enhance radiosensitivity, although COX-2 inhibitors-related cardiotoxicity may potentially affect its use. Further in-depth investigation of these drug combinations is needed to maximize antitumor efficacy and minimize the side effects.