Couto Mafalda R, Gonçalves Pedro, Catarino Telmo A, Martel Fátima
Department of Biochemistry, Faculty of Medicine and Institute for Research and Innovation in Health Sciences, University of Porto, Porto, Portugal.
Innate Immunity Unit, Institute Pasteur, French National Institute of Health and Medical Research (INSERM), U668, Paris, France.
Cell J. 2017 Spring;19(Suppl 1):96-105. doi: 10.22074/cellj.2017.4859. Epub 2017 May 17.
Colorectal cancer (CRC) is the second leading cause of cancer death in occidental countries. Chronic inflammatory bowel disease (crohn's disease and ulcerative colitis) is associated with an increased risk for CRC development. The aim of this work was to investigate the relationship between inflammatory status and absorption of nutrients with a role in CRC pathogenesis.
In this experimental study, we evaluated the effect of tumour necrosis factor-alpha (TNF-α), interferon-γ (IF-γ), and acetylsalicylic acid on 14C-butyrate (14C- BT), 3H-folic acid (3H-FA) uptake, and on proliferation, viability and differentiation of Caco-2 and IEC-6 cells in culture.
The proinflammatory cytokines TNF-α and INF-γ were found to decrease uptake of a low concentration of 14C-BT (10 µM) by Caco-2 (tumoral) and IEC-6 (normal) intestinal epithelial cell lines. However, the effect of TNF-α and INF-γ in IEC-6 cells is most probably related to a cytotoxic and antiproliferative impact. In contrast, INF-γ increases uptake of a high concentration (10 mM) of 14C-BT in Caco-2 cells. The anticarcinogenic effect of BT (10 mM) in these cells is not affected by the presence of this cytokine. On the other hand, acetylsalicylic acid stimulates 14C-BT uptake by Caco-2 cells and potentiates its antiproliferative effect. Finally, both TNF-α and INF-γ cause a significant decrease in 3H-FA uptake by Caco-2 cells.
The inflammatory status has an impact upon cellular uptake of BT and FA, two nutrients with a role in CRC pathogenesis. Moreover, the anti-inflammatory acetylsalicylic acid potentiates the anticarcinogenic effect of BT in Caco-2 cells by increasing its cellular uptake.
在西方国家，结直肠癌（CRC）是癌症死亡的第二大主要原因。慢性炎症性肠病（克罗恩病和溃疡性结肠炎）与CRC发生风险增加有关。本研究旨在探讨炎症状态与在CRC发病机制中起作用的营养物质吸收之间的关系。
在本实验研究中，我们评估了肿瘤坏死因子-α（TNF-α）、干扰素-γ（IF-γ）和乙酰水杨酸对培养的Caco-2和IEC-6细胞摄取14C-丁酸盐（14C-BT）、3H-叶酸（3H-FA）的影响，以及对细胞增殖、活力和分化的影响。
发现促炎细胞因子TNF-α和INF-γ可降低Caco-2（肿瘤性）和IEC-6（正常）肠上皮细胞系对低浓度14C-BT（10 μM）的摄取。然而，TNF-α和INF-γ对IEC-6细胞的作用很可能与细胞毒性和抗增殖作用有关。相反，INF-γ可增加Caco-2细胞对高浓度（10 mM）14C-BT的摄取。BT（10 mM）在这些细胞中的抗癌作用不受该细胞因子存在的影响。另一方面，乙酰水杨酸可刺激Caco-2细胞摄取14C-BT并增强其抗增殖作用。最后，TNF-α和INF-γ均导致Caco-2细胞对3H-FA的摄取显著降低。
炎症状态对BT和FA的细胞摄取有影响，这两种营养物质在CRC发病机制中起作用。此外，抗炎药物乙酰水杨酸通过增加BT在Caco-2细胞中的细胞摄取来增强其抗癌作用。
