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Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Review Article

COX-2 in Radiotherapy: A Potential Target for Radioprotection and Radiosensitization

Author(s): Mohsen Cheki, Rasoul Yahyapour, Bagher Farhood, Abolhassan Rezaeyan, Dheyauldeen Shabeeb, Peyman Amini, Saeed Rezapoor and Masoud Najafi*

Volume 11, Issue 3, 2018

Page: [173 - 183] Pages: 11

DOI: 10.2174/1874467211666180219102520

Price: $65

Abstract

Background: Each year, millions of people die from cancer. Radiotherapy is one of the main treatment strategies for cancer patients. Despite the beneficial roles of treatment with radiation, several side effects may threaten normal tissues of patients in the years after treatment.

Discussion: Moreover, high incidences of second primary cancers may reduce therapeutic ratio of radiotherapy. The search for appropriate targets of radiosensitization of tumor cells as well as radioprotection of normal tissues is one of the most interesting aims in radiobiology. Cyclooxygenase-2 (COX-2), as an inflammatory mediator has attracted interests for both aims. COX-2 activity is associated with ROS production and inflammatory signs in normal tissues. These effects further amplify radiation toxicity in irradiated cells as well as adjacent cells through a phenomenon known as Bystander effect. Increased COX-2 expression in distant non-irradiated tissues causes oxidative DNA damage and elevated cancer risk. Moreover, in tumors, the activation of this enzyme can increase resistance of malignant cells to radiotherapy. Hence, the inhibition of COX-2 has been proposed for better therapeutic response and amelioration of normal tissues. Celecoxib is one of the most studied COX-2 inhibitor for radiosensitization and radioprotection, while some other inhibitors have shown interesting results.

Conclusion: In this review, we describe the role of COX-2 in radiation normal tissue injury as well as irradiated bystander and non-targeted cells. In addition, mechanisms of COX-2 induced tumor resistance to radiotherapy and the potential role of COX-2 inhibition are discussed.

Keywords: COX-2, radiotherapy, radioprotection, radiosensitization, inflammation, Bystander effect, non-targeted effect, cancer, carcinogenesis.

Graphical Abstract


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