Chemopreventive efficacy of 25-hydroxyvitamin D3 in colon cancer.
Chemopreventive efficacy of 25-hydroxyvitamin D3 in colon cancer.
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25-羟基维生素 D3 对结肠癌的化学预防功效。
DOI：
10.1016/j.jsbmb.2006.12.074
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Mehta,RajendraG
中科院分区：
文献类型：
--
作者：
Murillo,Genoveva;Matusiak,Damien;Benya,RichardV;Mehta,RajendraG
Recently, it has been reported that 25-hydroxyvitamin D3-1α-hydroxylase [1α(OH)ase, CYP27B1], required to convert non-toxic 25-hyxdroxyvitamin D3 [25(OH)D3] to its active metabolite [1α,25(OH)2D3], is present in the epithelial cells of the human colon. In the present study, the potential chemoprotective role of 25(OH)D3was evaluated for colon cancer using the HT-29, human colon cancer cell line. Colon cancer cells were treated with 25(OH)D3(500nM or 1μM), 1α,25(OH)2D3(500nM), cholecalciferol (D3, 1μM) or vehicle and cell number determined at days 2 and 5 post-treatment. Results showed that both 25(OH)D3and 1α,25(OH)2D3induced dose- and time-dependent anti-proliferative effects on the HT-29 cells, with maximum inhibition noted at day 5. Western blot analyses revealed an up-regulation of VDR and 1α(OH)ase expression following 24h of treatment with 25(OH)D3, and 1α,25(OH)2D3. These results are consistent with the expression of VDR and 1α(OH)ase in samples of normal colonic tissue, aberrant crypt foci (ACFs) and colon adenocarcinomas. The VDR expression was sequentially increased from normal to pre-cancerous lesions to well-differentiated tumors and then decreased in poorly differentiated tumors. Expression of 1α(OH)ase was equally expressed in normal, pre-cancerous lesions and malignant human colon tissues. The increased expression of 1α(OH)ase in colon cancer cells treated with the pro-hormone and its anti-proliferative effects, suggest that 25(OH)D3may offer possible therapeutic and chemopreventive option in colon cancer.
