School of Life Sciences, Liaoning University, Shenyang 110036, China.
J Hematol Oncol. 2013 Jan 17;6:8. doi: 10.1186/1756-8722-6-8.
Both selenium and non-steroidal anti-inflammatory drug (NSAID) sulindac are effective in cancer prevention, but their effects are affected by several factors including epigenetic alterations and gene expression. The current study was designed to determine the effects of the combination of selenium and sulindac on tumor inhibition and the underlying mechanisms.
We fed the intestinal tumor model Apc/p21 mice with selenium- and sulindac-supplemented diet for 24 weeks, and found that the combination of selenium and sulindac significantly inhibited intestinal tumorigenesis, in terms of reducing tumor incidence by 52% and tumor multiplicities by 80% (p<0.01). Mechanistic studies revealed that the combination of selenium and sulindac led to the significant induction of the expression of p27 and p53 and JNK1 phosphorylation, and led to the suppression of β-catenin and its downstream targets. Impressively, the data also showed that demythelation on p21 promoter was associated with tumor inhibition by the combination of selenium and sulindac.
The selenium is synergistic with sulindac to exert maximal effects on tumor inhibition. This finding provides an important chemopreventive strategy using combination of anti-cancer agents, which has a great impact on cancer prevention and has a promising translational potential.
硒和非甾体抗炎药（NSAID）舒林酸在癌症预防方面都有效，但它们的效果受到多种因素的影响，包括表观遗传改变和基因表达。本研究旨在确定硒和舒林酸联合使用对肿瘤抑制的影响及其潜在机制。
我们用含硒和舒林酸的饮食喂养肠道肿瘤模型 Apc/p21 小鼠 24 周，发现硒和舒林酸联合使用可显著抑制肠道肿瘤发生，降低肿瘤发生率 52%，肿瘤数量减少 80%（p<0.01）。机制研究表明，硒和舒林酸联合使用可显著诱导 p27 和 p53 的表达以及 JNK1 磷酸化，并抑制β-catenin 及其下游靶标。令人印象深刻的是，数据还表明，p21 启动子的去甲基化与硒和舒林酸联合抑制肿瘤有关。
硒与舒林酸协同作用，对肿瘤抑制有最大效果。这一发现为使用抗癌药物联合提供了重要的化学预防策略，对癌症预防有重大影响，具有广阔的转化潜力。
