非甾体类抗炎药抗肿瘤作用的分子机制

该文从非甾体类抗炎药(NSAIDs)的抗肿瘤作用入手,结合近年来的国外最新文献和我们的研究结果,概要介绍了NSAIDs抗肿瘤作用的可能分子基础。NSAIDs抗肿瘤作用机制因肿瘤的种类而有所不同,它可通过抑制在某些肿瘤发生过程中异常表达的环氧化酶2(COX2),减少前列腺素E2等的生物合成,通过调节相关下游基因蛋白的表达,抑制肿瘤新生血管生成、阻止肿瘤细胞增殖并促进其凋亡。它也可作为过氧化酶体增殖激动剂受体γ(PPARγ)的激动剂,诱导某些肿瘤细胞内COX2的表达,促进环戊烯酮前列腺素(cyPGs)的生物合成,通过后者介导PPARγ依赖性或PPARγ非依赖性的促进肿瘤细胞凋亡作用。由于NSAIDs对肿瘤细胞抗增殖、促凋亡的特殊作用机制,与其他抗肿瘤治疗可能产生明显的协同作用。

The anti-tumor molecular mechanisms of non-steroid anti-inflammatory drugs

This review introduced the anti-tumor effects of non-steroid anti-inflammatory drugs (NSAIDs) and summarized their possible molecular mechanisms according to recent abroad literatures and our research results. Some evidence showed that the anti-tumor mechanisms of NSAIDs were different in various tumors.NSAIDs decreased the biosynthesis of PGE_2 and regulated the expressions of downstream correlated genes and proteins through restraining abnormal expression of COX-2 in certain neoplasms,which resulted in the inhibition of tumor angiogenesis and proliferation as well as induced apoptosis. But in other cancer cells, NSAIDs, as activators of peroxisome proliferator-activated receptor γ (PPARγ), induced COX-2 expression, promoted the biosynthesis of cyclopentenone prostaglandins (cyPGs). cyPGs further induced tumor cell apoptosis with PPARγ dependently or PPARγ independently. Since their special mechanisms of anti-proliferation and pro-apoptosis, NSAIDs revealed significant synergistic effects with other anti-tumor treatments.