Restoration of the anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D by silibinin in vitamin D-resistant colon cancer cells.
Restoration of the anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D by silibinin in vitamin D-resistant colon cancer cells.
复制标题
DOI：
10.1016/j.canlet.2015.03.042
复制
发表时间：
2015-07-01
期刊：
影响因子：
9.7
通讯作者：
Falzon, Miriam
中科院分区：
文献类型：
--
作者：
Bhatia, Vandanajay;Falzon, Miriam
结直肠癌（CRC）是发达国家第三大常见癌症。大部分病例与慢性肠道炎症有关，伴随TNF-α释放增加和Snail 1/Snail 2水平升高。这些转录因子反过来又抑制维生素D受体（VDR）的表达，导致对1，25-二羟基维生素D（1，25 D）的保护性抗增殖和抗迁移作用的反应性丧失。实验和流行病学证据支持使用天然产品来靶向CRC。在此，我们发现黄酮木脂素水飞蓟宾逆转了TNF-α诱导的1，25 D耐药人结肠癌细胞HT-29中Snail 1和Snail 2的上调。这些水飞蓟宾效应伴随着VDR水平的增加; Snail 1过表达逆转了这些水飞蓟宾效应。水飞蓟宾也恢复启动子活性的维生素D反应元件（VDRE）报告构建体。虽然1，25 D对HT-29和SW 480-R细胞的增殖和迁移没有显著影响，但与水飞蓟宾共同处理恢复了1，25 D的反应性。此外，与水飞蓟宾加1，25 D的共同治疗在单独的水飞蓟宾没有效果的剂量下降低了增殖和迁移。这些发现表明，这种组合可能提供了一种新的方法来靶向慢性结肠炎症条件下的CRC。
Colorectal carcinoma (CRC) is the third most common cancer in developed countries. A large fraction of cases are linked to chronic intestinal inflammation, with concomitant increased TNF-α release and elevated Snail1/Snail2 levels. These transcription factors in turn suppress vitamin D receptor (VDR) expression, resulting in loss of responsiveness to the protective anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D (1,25D). Experimental and epidemiologic evidence support the use of natural products to target CRC. Here we show that the flavonolignan silibinin reverses the TNF-α-induced upregulation of Snail1 and Snail2 in the 1,25D-resistant human colon carcinoma cells HT-29. These silibinin effects are accompanied by an increase in VDR levels; Snail1 overexpression reverses these silibinin effects. Silibinin also restores promoter activity from a vitamin D-response element (VDRE) reporter construct. While 1,25D had no significant effect on HT-29 and SW480-R cell proliferation and migration, co-treatment with silibinin restored 1,25D responsiveness. In addition, co-treatment with silibinin plus 1,25D decreased proliferation and migration at doses where silibinin alone had no effect. These findings demonstrate that this combination may present a novel approach to target CRC in conditions of chronic colonic inflammation.
登录
查看更多内容
影响因子：
3.6
作者：
Bobilev, Irene;Novik, Victoria;Danilenko, Michael
通讯作者：
Danilenko, Michael
影响因子：
5.6
作者：
Bezdekova M;Brychtova S;Sedlakova E;Langova K;Brychta T;Belej K
通讯作者：
Belej K
影响因子：
4.7
作者：
Kallay, E;Pietschmann, P;Cross, HS
通讯作者：
Cross, HS
影响因子：
8
作者：
Dhanalakshmi, S;Singh, RP;Agarwal, R
通讯作者：
Agarwal, R
影响因子：
3.2
作者：
Horvath, Henrik C.;Lakatos, Peter;Kallay, Enikoe
通讯作者：
Kallay, Enikoe