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

(背景)几篇综述总结了环氧合酶2选择性抑制剂的使用可以预防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不清楚。对切除的结肠癌标本进行组织学检查，发现淋巴小叶或免疫细胞(CTL NK细胞)位于结肠癌附近。研究COX2及其副产物和COX2抑制剂对免疫系统的影响可能是有用的，因为这些免疫细胞(CTL NK细胞)可能具有抗肿瘤作用。解释COX2选择性抑制剂对免疫系统功能的影响将导致结肠癌的化学预防，因为COX2在结肠癌的早期就有表达。(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(细胞凋亡)的影响。此外，COX2或COX2抑制剂对MU…的影响结肠癌与免疫细胞之间的关系也得到了进一步的研究。(方法)用COX2选择性抑制剂(+)或(-)培养COX2阳性结肠癌细胞株(HCA7)和阴性结肠癌细胞株(HCT116)，检测TRAIL-DR、Fas-FASL的表达。共培养12h后，FACScan流式细胞仪检测结肠癌细胞对免疫细胞的影响(细胞凋亡、坏死)。(结果)HCA7和HCT116均可识别FASL和TRAIL的表达。Fas和DR4主要表达于Jurkat细胞。当Jurkat细胞与HCA7细胞共同培养时，Jurkat细胞发生了细胞损伤(细胞凋亡和坏死)。另一方面，HCA7与COX2抑制剂预先孵育后，细胞损伤(细胞凋亡和坏死)减少。(结论)COX2抑制剂减轻结肠癌细胞对免疫细胞的损伤作用可能是其阻止腺瘤性息肉生长或现有息肉进展的可能机制。较少

(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