Effects of vitamin D and calcium supplementation on markers of apoptosis in normal colon mucosa: a randomized, double-blind, placebo-controlled clinical trial.
Effects of vitamin D and calcium supplementation on markers of apoptosis in normal colon mucosa: a randomized, double-blind, placebo-controlled clinical trial.
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DOI：
10.1158/1940-6207.capr-08-0157
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Dash C
中科院分区：
文献类型：
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作者：
Fedirko V;Bostick RM;Flanders WD;Long Q;Shaukat A;Rutherford RE;Daniel CR;Cohen V;Dash C
为了进一步阐明和/或开发钙和维生素D作为人类结直肠癌的化学预防药物，了解这些药物降低疾病风险的机制，并开发结直肠癌风险的“可治疗”生物标记物，我们进行了一项试点、随机、双盲、安慰剂对照、2×2因素临床试验，以测试钙和维生素D3单独和联合使用对正常大肠粘膜细胞凋亡标记物的影响。92名患有至少一个病理证实的结直肠腺瘤的男性和女性接受了钙2.0克/天或维生素D3800IU/天的治疗，与安慰剂相比，治疗持续了6个月。采用自动免疫组织化学方法检测正常直肠黏膜组织中细胞凋亡抑制因子Bcl2和促凋亡因子Bax的表达及在大肠隐窝中的分布，并进行图像分析。治疗6个月后，与安慰剂组相比，维生素D组隐窝全长Bax的表达增加了56%(p=0.02)，钙组(p=0.31)和钙加维生素D组(p=0.36)增加了33%。维生素D的治疗效果在隐窝的上40%或分化区更为明显(80%；p=0.01)。对Bcl2表达的影响无统计学意义。总体而言，这些初步结果表明，钙和维生素D单独或联合使用可能会促进正常人类结肠上皮细胞的凋亡，最强的治疗作用可能是与维生素D相关的和结肠隐窝的上部。
To further clarify and/or develop calcium and vitamin D as chemopreventive agents against colorectal cancer in humans, understand the mechanisms by which these agents reduce risk for the disease, and develop ‘treatable’ biomarkers of risk for colorectal cancer, we conducted a pilot, randomized, double-blind, placebo-controlled, 2×2 factorial clinical trial to test the effects of calcium and vitamin D3, alone and in combination on markers of apoptosis in the normal colorectal mucosa. Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with calcium 2.0 g/day or vitamin D3 800 IU/day, alone or in combination vs. placebo over six months. Overall expression and colorectal crypt distributions of Bcl-2 (an apoptosis inhibitor) and Bax (an apoptosis promoter), in biopsies of normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. After six months treatment, Bax expression along the full lengths of crypts increased 56% (p=0.02) in the vitamin D group, and 33% in both the calcium (p=0.31) and calcium plus vitamin D (p=0.36) groups relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40%, or differentiation zone, of crypts (80%; p=0.01). There were no statistically significant treatment effects on Bcl-2 expression. Overall, these preliminary results suggest that calcium and vitamin D, individually or together, may enhance apoptosis in the normal human colorectal epithelium, and the strongest treatment effects may be vitamin D related and in the upper sections of the colorectal crypts.