The role of COX2 and its byproducts as a modulator of tumor-immuno system

COX2及其副产物作为肿瘤免疫系统调节剂的作用

• 批准号: 14570508
• 负责人: KOBAYASHI Osamu
• 金额: $ 1.86万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570508/
• 关键词: Colon cancer; Immune system; COX2 selective inhibitor; FASL; TRAIL; chemoprevention; Jurkat cell; HCA7; 大腸癌細胞; 腫瘍免疫; cycloxygenase 2; apoptosis; サイクロオキシゲナーゼ2; プロスタグランジン

(Background) Several reviews have summarized that the use of cyclooxygenase2 selective inhibitor prevents growth of adenomatous polyps or progression of existing polyps. Despite these positive findings, the mechanism how these drugs act is not well understood. As resected colon cancer specimen was examined histlogically, lymphod folicular or immune cells (CTL NKcells) are located at the adjacent to the colon neoplasm. It might be useful to investigate the effects of COX2, its by-products and COX2 inhibitor on immune system because those immune cells (CTL NKcells) might have an anti-tumor effects. To explain the effects of COX2 selective inhibitor on function of immune system will lead to the chemoprevention of colon cancer, as COX2 is expressed at the early stage of colon neoplasm. (Purpose) The effects of colon cancer cells on the function of lymphocyte (FAS-FASL TRAIL-DR) and on the damage of immune cells (apoptosis) were examined. Moreover the effects of COX2 or COX2 inhibitor on mu … More tual relationship between colon cancer and immune cells also investigated. (Method) COX2 positive colon cancer cell line (HCA7) and negative cell line (HCT116) were cultured under the condition of COX2 selective inhibitor (+) or (-), then the expression of TRAIL-DR FAS-FASL of those cell lines were investigated. 12 hrs after the co-culture, the effect of colon cancer cells on immune cells (apoptosis necrosis) was examined using FACScan flow cytometer. (Results) The expression of FASL and TRAIL was recognized both HCA7 and HCT116. FAS and DR4 was mainly expressed in Jurkat cell. As Jurkat cell was co-cultured with HCA7 cell, cell damage (apoptosis and necrosis) was induced in Jurkat cell. On the other hands cell damage (apoptosis and necrosis) was decreased as HCA7 was preincubated with COX2 inhibitor. (Conclusion) The effects of COX2 inhibitor that attenuate the damage of immune cells induced by colon cancer cell was assumed as a possible mechanism how COX2 inhibitor prevents the growth of adenomatous polyps or progression of existing polyps. Less

（背景）一些综述总结了使用环氧化酶2选择性抑制剂可以防止腺瘤性息肉的生长或现有息肉的进展。尽管有这些积极的发现，但这些药物的作用机制尚未得到很好的理解。结肠癌切除标本经组织学检查，淋巴样滤泡或免疫细胞（CTL NK细胞）位于结肠肿瘤附近。研究COX 2及其副产物和COX 2抑制剂对免疫系统的影响可能是有益的，因为这些免疫细胞（CTL NK细胞）可能具有抗肿瘤作用。COX 2在结肠癌的早期就有表达，阐明COX 2选择性抑制剂对免疫系统功能的影响将有助于结肠癌的化学预防。（目的）探讨结肠癌细胞对淋巴细胞功能（FAS-FASL、TRAIL-DR）和免疫细胞损伤（凋亡）的影响。此外，COX 2或COX 2抑制剂对小鼠的影响也是非常重要的。 ...更多信息 结肠癌和免疫细胞之间的实际关系也进行了研究。（方法）将COX 2选择性抑制剂（+）或（-）作用于COX 2阳性结肠癌细胞系（HCA 7）和COX 2阴性结肠癌细胞系（HCT 116），观察其TRAIL-DR FAS-FASL表达的变化。共培养12小时后，使用FACScan流式细胞仪检查结肠癌细胞对免疫细胞的影响（凋亡坏死）。（结果）FASL和TRAIL在HCA 7和HCT 116中均有表达。FAS和DR 4主要表达于Jurkat细胞。当Jurkat细胞与HCA 7细胞共培养时，在Jurkat细胞中诱导细胞损伤（凋亡和坏死）。另一方面，细胞损伤（凋亡和坏死）随着HCA 7与COX 2抑制剂预孵育而减少。结论COX 2抑制剂减轻结肠癌细胞对免疫细胞的损伤可能是COX 2抑制剂抑制结肠腺瘤性息肉生长或已有息肉进展的机制之一。少