Suppr超能文献

抑制核因子-κB可增强结肠癌对5-氟尿嘧啶/亚叶酸的敏感性。

Inhibition of NF-kappa B augments sensitivity to 5-fluorouracil/folinic acid in colon cancer.

作者信息

Voboril Rene, Hochwald Steven N, Li Jing, Brank Adam, Weberova Jana, Wessels Frank, Moldawer Lyle L, Camp E Ramsay, MacKay Sally L D

机构信息

Department of Surgery, Division of Surgical Oncology, University of Florida College of Medicine, 1600 SW Archer Road, Room 6184, Gainesville, FL 32610, USA.

出版信息

J Surg Res. 2004 Aug;120(2):178-88. doi: 10.1016/j.jss.2003.11.023.

Abstract

BACKGROUND

5-fluorouracil (5-FU), the most common antimetabolite used for the treatment of colorectal cancer, exerts its cytotoxic effects through the induction of apoptosis. Folinic acid potentiates the effect of 5-FU. Drug activity is currently limited as a result of inducible chemoresistance. Limited research suggests that the transcription factor nuclear factor kappa-B (NF-kappaB), which has antiapoptotic properties, may play a major role in inducible chemoresistance.

MATERIALS AND METHODS

SW48 colon cancer cells were used for all experiments. Cell growth was determined by cell proliferation assay. Apoptosis was assessed by measuring caspase 3 activity. Activation of NF-kappaB was ascertained by electrophoretic mobility shift assay, luciferase reporter assay, and Western blot analysis.

RESULTS

Treatment with 5-FU (0.001-10 mm), not only inhibited growth and induced apoptosis but significantly activated NF-kappaB in SW48 cells. Folinic acid alone (0.01-100 mg/L) did not inhibit growth but improved the cytotoxic effect of 5-FU in a dose-dependent manner. Likewise, folinic acid alone did not activate NF-kappaB or induce apoptosis but enhanced 5-FU-mediated NF-kappaB activation and cell apoptosis. Transfection with adenovirus IkappaBalpha super-repressor strongly inhibited constitutive activation of NF-kappaB and significantly enhanced 5-FU and 5-FU/Folinic acid-mediated growth inhibition (P < 0.05).

CONCLUSIONS

Treatment with 5-FU activates NF-kappaB. Folinic acid enhances 5-FU-mediated activation of NF-kappaB. Inhibition of NF-kappaB enhances the cytotoxic effect of 5-FU with or without Folinic acid in colon cancer cells.

摘要

背景

5-氟尿嘧啶(5-FU)是治疗结直肠癌最常用的抗代谢药物,通过诱导细胞凋亡发挥其细胞毒性作用。亚叶酸可增强5-FU的作用。由于可诱导的化疗耐药性,目前药物活性受到限制。有限的研究表明,具有抗凋亡特性的转录因子核因子κB(NF-κB)可能在诱导化疗耐药中起主要作用。

材料与方法

所有实验均使用SW48结肠癌细胞。通过细胞增殖试验测定细胞生长情况。通过测量半胱天冬酶3活性评估细胞凋亡。通过电泳迁移率变动分析、荧光素酶报告基因分析和蛋白质免疫印迹分析确定NF-κB的激活情况。

结果

用5-FU(0.001-10 mM)处理,不仅抑制了SW48细胞的生长并诱导其凋亡,还显著激活了NF-κB。单独使用亚叶酸(0.01-100 mg/L)不会抑制生长,但以剂量依赖的方式增强了5-FU的细胞毒性作用。同样,单独使用亚叶酸不会激活NF-κB或诱导凋亡,但增强了5-FU介导的NF-κB激活和细胞凋亡。用腺病毒IκBα超级抑制剂转染可强烈抑制NF-κB 的组成性激活,并显著增强5-FU和5-FU/亚叶酸介导的生长抑制作用(P < 0.05)。

结论

5-FU处理可激活NF-κB。亚叶酸增强5-FU介导的NF-κB激活。抑制NF-κB可增强5-FU在有或没有亚叶酸存在时对结肠癌细胞的细胞毒性作用。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验