选择性COX-2抑制剂在胶质瘤放疗中的研究进展

Progress of the study on selective COX-2 inhibitors in the radiotherapy of glioma

环氧合酶(cyclooxygenase,COX)又名前列腺素内过氧化物合成酶,是前列腺素类似物合成的限速酶。COX-2是其诱导型酶。胶质瘤中COX-2的高表达被认为与肿瘤的侵袭性、预后相关。COX-2在胶质瘤的发生发展过程中发挥重要作用。选择性COX-2抑制剂通过直接和间接的作用机制而成为放射增敏剂。它们通过直接作用肿瘤细胞增强放射反应性,同时间接通过前列腺素影响肿瘤的血管形成抑制肿瘤生长。在体内和体外的研究表明选择性COX-2抑制荆可以增强胶质瘤对放射的反应性,降低恶性胶质瘤患者术后放射的必需照射剂量。而且在提高肿瘤放射敏感性的同时不增加对正常组织的放射损伤,甚至对正常组织有放射保护作用。因此,放疗联合选择性COX-2抑制剂可能成为胶质瘤治疗的新的有效途径。

The cyclooxygenase enzyme（COX）,prostaglandin endoperoxide synthesis enzyme, is the rate- limiting enzyme in the synthesis of prostaglandin. COX - 2 is its induced - enzyme. COX - 2 overexpression has been associated with tumor aggressiveness and prognosis. COX - 2 plays an important role in the progress of glioma. Selective COX - 2 inhbitors act as radiosensitizer by direct and indirect mechanisms of action in tumor treatment. They enhance radioresponse by direct actions on tumor cells, and they has also shown to act indirectly to inhibit the ability of tumor growth by effecting tumor vasculature. In vitro and in vovo studies show selective COX - 2 inhbitors enhance the response of glioma to irradiation, and can lower the required doses of postoperative radiation, Selective COX - 2 inhbitors protect the normal tissue form radioactive lesions at the time of enhancing tumors＇ radioresponse. For all these reasons,radiotherapy combined with selective COX - 2 inhbitors may be a new effective approach to the treatment of glioma.