内源性集落刺激因子与人结肠癌细胞凋亡之间的关系：环氧化酶抑制剂的作用

Relationship between endogenous colony stimulating factors and apoptosis in human colon cancer cells: role of cyclo-oxygenase inhibitors.

作者信息

Calatayud S, Warner T D, Breese E J, Mitchell J A

机构信息

Unit of Critical Care, The Royal Brompton and Harefield N.H.S. Trust, Imperial College School of Medicine, Sydney Street, London SW 6NP.

出版信息

Br J Pharmacol. 2001 Nov;134(6):1237-44. doi: 10.1038/sj.bjp.0704358.

DOI:10.1038/sj.bjp.0704358

PMID:11704643

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1573049/

Abstract

Nonsteroidal anti-inflammatory drug (NSAID) usage is associated with gastrointestinal inflammatory damage and aggravation of gut inflammatory conditions. NSAIDs also exert a preventive effect against colon cancer that seems to be due to increased colon cell apoptosis. NSAIDs have been shown to modulate the release of colony stimulating factors (CSFs) in some cells. In the present study we analysed the effect of these drugs on secretion of CSFs and apoptosis in human colon epithelial cells (HT-29). 2. HT-29 cells secreted bioactive levels of GM-CSF, G-CSF and M-CSF when stimulated with IL-1ss and TNF-alpha, and diclofenac (10(-7)-10(-4) M), indomethacin (10(-7)-10(-4) M) and sodium salicylate (10(-5)-10(-2) M) induced concentration-dependent increases in GM-CSF secretion. 3. Reduced secretion of G-CSF and M-CSF and increased cell apoptosis were observed with the highest concentrations of these non-selective NSAIDs. 4. No changes in any CSF release or HT-29 cell apoptosis were detected in the presence of the COX-2 selective inhibitor DFP (10(-7)-10(-4) M). 5. Neither the exogenous addition of CSFs nor the blockade of secreted CSFs modified apoptosis in HT-29 cells stimulated with cytokines and/or NSAIDs. 6. These results suggest that colon epithelial cells can contribute to local inflammatory responses by releasing CSFs and thus extend the life span of local leukocytes. Modulation of CSF levels by non-selective NSAIDs may be involved in the pro-inflammatory effects of these agents in the gut.

摘要

非甾体抗炎药（NSAID）的使用与胃肠道炎症损伤及肠道炎症状况的加重有关。NSAIDs 对结肠癌也具有预防作用，这似乎是由于结肠细胞凋亡增加所致。已表明 NSAIDs 可调节某些细胞中集落刺激因子（CSF）的释放。在本研究中，我们分析了这些药物对人结肠上皮细胞（HT - 29）中 CSF 分泌及细胞凋亡的影响。2. 用白细胞介素 - 1β（IL - 1β）和肿瘤坏死因子 - α（TNF - α）刺激时，HT - 29 细胞分泌生物活性水平的粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）、粒细胞集落刺激因子（G - CSF）和巨噬细胞集落刺激因子（M - CSF），双氯芬酸（10⁻⁷ - 10⁻⁴ M）、吲哚美辛（10⁻⁷ - 10⁻⁴ M）和水杨酸钠（10⁻⁵ - 10⁻² M）诱导 GM - CSF 分泌呈浓度依赖性增加。3. 这些非选择性 NSAIDs 的最高浓度可导致 G - CSF 和 M - CSF 分泌减少及细胞凋亡增加。4. 在存在 COX - 2 选择性抑制剂双氟尼酸（DFP，10⁻⁷ - 10⁻⁴ M）的情况下，未检测到任何 CSF 释放或 HT - 29 细胞凋亡的变化。5. 外源性添加 CSF 或阻断分泌的 CSF 均未改变用细胞因子和/或 NSAIDs 刺激的 HT - 29 细胞中的细胞凋亡。6. 这些结果表明，结肠上皮细胞可通过释放 CSF 促进局部炎症反应，从而延长局部白细胞的寿命。非选择性 NSAIDs 对 CSF 水平的调节可能与这些药物在肠道中的促炎作用有关。