选择性环氧合酶2抑制剂对肿瘤放化疗增敏作用研究进展

环氧合酶2(COX-2)与肿瘤关系密切.临床前期研究显示,选择性COX-2抑制剂能增强肿瘤的放射敏感性作用和化疗药物的抗肿瘤活性,选择性COX-2抑制剂有可能为肿瘤预防和治疗提供新方法和途径.     

选择性环氧合酶2抑制剂对肿瘤放化疗增敏作用研究进展

环氧合酶2(COX-2)与肿瘤关系密切.临床前期研究显示,选择性COX-2抑制剂能增强肿瘤的放射敏感性作用和化疗药物的抗肿瘤活性,选择性COX-2抑制剂有可能为肿瘤预防和治疗提供新方法和途径.     

COX-2和mPGEs-1与肿瘤关系的研究进展

目的:总结COX-2和mPGEs-1的生物学作用以及肿瘤的研究进展,探讨COX-2和mPGEs-1选择性抑制剂在肿瘤治疗中的作用,为癌症的临床治疗提供参考.方法:利用PubMed数据库检索系统,以"COX-2、mPGEs-1、肿瘤"为关键词,检索到相关文献785篇,排除与本研究无关的文献,再将COX-2、mPGEs-1的生物学作用、COX-2和mPGEs-1选择性抑制荆、肿瘤作为纳入标准,最后选出相关文献23篇.结果:COX-2和mPGEs-1在多种肿瘤中高表述,与多种细胞因子以及前列腺素家族的其他成员相互作用,构成一个复杂的网络系统,调节肿瘤以及周围血管内皮细胞的生长,在常规抗肿瘤治疗的同时,协同和辅助应用抗COX-2中和抗体会改善肿瘤的治疗效果.结论:COX-2-mPGES-1作为新型的肿瘤治疗靶点,成为一条更安全、更理想的干预途径,在肿瘤临床治疗中必将显示其治疗价值和意义.     

选择性环氧合酶-2抑制剂nimesulide对人类乳腺癌肿瘤血管形成因子的影响

目的 探讨选择性环氧合酶-2(COX-2)抑制剂nimesulide对乳腺癌肿瘤血管形成因子的影响.方法 利用体外培养的乳腺癌MDA-MB-231细胞株;应用免疫组织化学、反转录聚合酶链反应(RT-PCR)、Western blotting观察不同浓度nimesulide对肿瘤血管形成因子COX-2、PGE2、VEGF、TGFβ1表达的影响.结果 nimesulide以剂量依赖性方式下调COX-2、VEGF基因及蛋白的表达水平,同时以剂量依赖性方式抑制MDA-MB-231细胞PGE2的合成,对TGFβ1的表达无明显影响.结论 选择性COX-2抑制剂nimesulide能下调乳腺癌MDA-MB-231细胞株肿瘤血管形成因子COX-2、PGE2、VEGF的表达,为选择性COX-2抑制剂用于乳腺癌的预防及治疗提供了实验依据.     

环氧合酶-2抑制剂在肿瘤防治中的作用

环氧合酶-2(COX-2)与肿瘤的发生发展密切相关,选择性COX-2抑制剂通过影响细胞的增殖、凋亡、细胞周期、肿瘤新生血管、侵袭和转移、机体免疫等多个方面而起到预防和治疗肿瘤的作用,还可以增强肿瘤的放化疗效果.因此,深入研究COX-2抑制剂与肿瘤的关系将为肿瘤预防和治疗提供新的靶点.     

环氧化酶-2与肝肿瘤

环氧化酶-2(COX-2)是环氧化酶的诱导型,是催化花生四烯酸合成前列腺素的限速酶.COX-2过表达与肝肿瘤有密切关系,其作用机制可能涉及多个方面.选择性COX-2抑制剂的深入研究有望使其在肝脏肿瘤的治疗方面有新的突破.     

环氧化酶-2与肿瘤关系的研究进展

环氧化酶-2(COX-2)是体内前列腺素(PG)合成过程中重要的限速酶,在多种人类肿瘤中有不同程度的表达,并且与肿瘤发生、肿瘤细胞增殖、凋亡、肿瘤新生血管形成以及肿瘤的转移等有关.选择性COX-2抑制剂有望成为有效的肿瘤预防和治疗的新靶点.     

环氧化酶-2与食管癌

环氧化酶-2(COX-2)在恶性肿瘤中的作用日趋受到重视,但其确切作用机制尚不清楚.COX-2高表达可通过抑制细胞凋亡、诱导肿瘤血管生成等途径促进食管癌的生长和浸润,选择性COX-2抑制剂的开发和应用有望为食管癌预防和治疗开辟新的途径.     

环氧化酶-2与食管癌的研究进展

环氧化酶-2(COX-2)在恶性肿瘤中的作用日益受到重视,多数食管癌COX-2蛋白高表达,与食管癌发生发展和预后密切相关.COX-2通过诱导肿瘤血管生成、促进细胞增殖、抑制细胞凋亡、增加肿瘤侵袭力、抑制免疫及诱导前致癌物的活性等机制促进食管癌的生长和浸润,选择性COX-2抑制剂的开发和应用有望为食管癌预防和治疗开辟新的途径,成为食管癌分子靶向治疗新的方向.     

环氧化酶-2抑制剂治疗胰腺癌机制研究进展

环氧化酶-2(COX-2)在胰腺癌发生、浸润和转移中起着重要作用,选择性COX-2抑制剂治疗胰腺癌的作用机制包括减少前列腺素的合成、抑制细胞增殖、诱导细胞凋亡和抑制肿瘤血管生成等.     

Selective cyclooxygenase (COX)-1 or COX-2 inhibitors control metastatic disease in a murine model of breast cancer

Using a highly metastatic mammary tumor cell line that expresses both cyclooxygenase (COX) isoforms, we now show that oral administration of either a selective COX-2 inhibitor (celecoxib) or a selective COX-1 inhibitor (SC560) to mice with established tumors results in significant inhibition of tumor growth. Administration of the dual inhibitor, indomethacin, leads to even better growth control. Metastatic capacity is also reduced by treatment of tumor-bearing mice with either COX-1 or COX-2 selective inhibitors. Pretreatment of tumor cells with COX inhibitors also reduces metastatic success, indicating that tumor cells may be a direct target of action by COX inhibitors. Growth of a second cell line, which does not express COX-2 in vivo, is also reduced by celecoxib, implicating both COX-dependent and COX-independent mechanisms.     

Overexpression of cyclooxygenase-2 is associated with radioresistance in oral squamous cell carcinoma

Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, is overexpressed in many types of malignant tumors, which in turn may stimulate tumor growth and protect against damage by irradiation or cytotoxic agents. The purpose of this study is to investigate the relationship between the radiation sensitivity and elevated level of COX-2. Radiation sensitivity of the eight oral SCC cell lines differed greatly in their response to radiation. Further, the level of the COX-2 expression correlated inversely with increased tumor radiation sensitivity. The similar significant association between the response to preoperative radiation therapy and COX-2 overexpression was observed in the oral SCC patients. In addition, treatment with a COX-2 selective inhibitor enhanced the radioresponse of HSC-2 cell, which constitutively expressed COX-2. These results suggested that COX-2 expression level correlates to radiation tolerance and the COX-2 selective inhibitor may be a potent enhancer for tumor radioresponse in oral SCC.     

Selective inhibition of cyclooxygenase (COX)-2 inhibits endothelial cell proliferation by induction of cell cycle arrest

High-level expression of cyclooxygenase (COX)-2 is reported in 80-90% of colorectal adenocarcinomas. Selective inhibition of COX-2 was shown to reduce colorectal tumorigenesis in different models of carcinogenesis and to prevent metastasis in xenograft tumor models, as well as to suppress in vitro induced angiogenesis. Recently, COX-2 was reported to be expressed not only in malignant epithelial cells, but also in the neovasculature that feeds the tumor in a variety of solid human cancers. Thus, one of the possible mechanisms by which selective COX-2 inhibitor reduces tumor growth and metastasis is through inhibition of tumor angiogenesis. Although a report suggested a possible role of endothelial COX-1 in the process of angiogenesis, in a recent study, the selective inhibition of COX-2 was shown to strongly inhibit angiogenesis by inducing endothelial cell (EC) apoptosis. In the present study, using human umbilical vein endothelial cells (HUVECs) as a model of angiogenesis, we investigated the potential antiangiogenic effect of the selective COX-2 inhibitor and its mechanism of action, and clearly demonstrated that selective inhibition of COX-2 caused a dose-dependent decrease in the proliferative activity of ECs, as well as an inhibition of capillary-like tube formation. The inhibitory effect on EC proliferation was dependent on the cell cycle arrest to the G1 phase and not on cell apoptosis.     

Potentiation of tumor response to radiation or chemoradiation by selective cyclooxygenase-2 enzyme inhibitors

Cyclooxygenase-2 (COX-2) is an enzyme expressed primarily in pathologic states, such as inflammatory disorders and cancer, where it mediates prostaglandin production. Its overexpression is associated with more aggressive biologic tumor behavior and adverse patient outcome. Increasing evidence shows that agents that selectively inhibit COX-2 enhance tumor response to radiation or chemotherapeutic agents. This article gives an overview of some of this evidence. In addition, we describe new results showing that celecoxib, a selective COX-2 inhibitor, enhanced response of A431 human tumor xenografts in nude mice to radiation by an enhancement factor (EF) of 1.43 and to the chemotherapeutic agent docetaxel by an EF of 2.07. Celecoxib also enhanced tumor response when added to the combined docetaxel plus radiation treatment (EF = 2.13). Further experiments showed that selective COX-2 inhibitors enhanced tumor cell sensitivity to ionizing radiation, involving inhibition of cellular repair from radiation damage and cell cycle redistribution as mechanisms for some cell types. The results show that selective COX-2 inhibitors have the potential to improve tumor radiotherapy or radiochemotherapy, and this therapeutic strategy is currently under clinical testing.     

The effects of non-selective, preferential-selective and selective COX-inhibitors on the growth of experimental and human tumors in mice related to prostanoid receptors

Earlier observations on cyclo-oxygenase inhibitors (NSAIDs) restricting tumor growth were re-evaluated by comparing the effects of non-selective, preferential selective and selective derivatives of COX-inhibitors on tumor growth in mouse models with either prostaglandin-sensitive (MCG-101, human tumors) and -insensitive transplants (K1735-M2). Tumor growth, with and without provision of a classical cyclo-oxygenase inhibitor (indomethacin), was related to tumor content of COX-1/COX-2 protein as well as to EP1-EP4 and prostacyclin receptor expression. Mouse serum amyloid protein (SAP) was measured as an indicator of systemic inflammation, which relates to pro-inflammatory cytokines. Indomethacin inhibited tumor growth and prolonged the survival of mice bearing MCG-101 tumors, which display a high production of PGE2, while K1735-M2 tumors with insignificant amounts of PGE2 did not respond to indomethacin at all. However, the effects of various NSAIDs on tumor growth were highly variable in combination with the fact that most preferential selective and selective COX-2 inhibitors attenuated poorly systemic inflammation evaluated by plasma concentrations of mouse SAP. The ability of NSAIDs to attenuate tumor growth was not related to the tumor content of COX-2 protein as expected. Multivariate analysis suggests that significant COX-inhibition of tumor growth may be related to tumor expression of subtype EP2, EP3 (p<0.005) and perhaps EP4 (p<0.09) in complex interplay. The extent of tumor growth inhibition by COX-inhibitors is not simply related to drug specificity on COX-1 or COX-2 pathways. Such effects may instead be related to tumor expression of prostanoid receptors in tumor tissue.     

Cyclooxygenase-2 (COX-2) enzyme inhibitors and radiotherapy: preclinical basis

Cyclooxygenase-2 (COX-2), an enzyme induced by proinflammatory cytokines, mitogenic substances, oncogenes, growth factors, and hypoxia, among others, is involved in the metabolic conversion of arachidonic acid to prostaglandins in inflamed tissues and neoplasia. COX-2 is often overexpressed in malignant tumors and premalignant lesions and is linked to carcinogenesis, maintenance of progressive tumor growth, and facilitation of metastatic spread. Because COX-2 may also be a determinant of tumor radioresistance, its inhibition or inhibition of its products (prostaglandins) may improve tumor response to radiotherapy. Preclinical studies have shown that treatment with selective COX-2 inhibitors significantly enhances tumor response to radiation without appreciably affecting normal tissue radioresponse. The underlying mechanisms of the COX-2 inhibitor-radiation interactions seem to be multiple, with the enzyme inhibitor directly or indirectly augmenting tumor cell destruction by radiation. Thus, use of selective COX-2 inhibitors is a potential approach for improving cancer radiotherapy.