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

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570508
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: JUNTENDO UNIVERSITY
• Principal Investigator: KOBAYASHI Osamu Juntendo University, School of Medicine, associate professor, 医学部, 講師 (80296871)
• Project Period (FY): 2002 – 2003
• Keywords: Colon cancer / Immune system / COX2 selective inhibitor / FASL / TRAIL / chemoprevention / Jurkat cell / HCA7

Research Abstract

(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 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.