Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line.
作者： M G Thomas , S Tebbutt , R C Williamson
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摘要: Like calcium, vitamin D may protect against colorectal neoplasia as it reduces epithelial cell proliferation and induces differentiation. Although its therapeutic use is limited by effects on calcium metabolism, analogues such calcipotriol produce little hypercalcaemia. Stathmokinetic immunohistochemical techniques were used to study the effect of 1,25 (OH)2 D3 in human rectal mucosa a colon cancer line. Paired sigmoidoscopic biopsy specimens obtained from 17 control patients five with familial adenomatous polyposis. Explants established organ culture, or without addition D. Proliferation was assessed using (1) metaphase arrest determine crypt production rate (CCPR) (2) Ki-67 monoclonal antibody directed an antigen present proliferating cells. concentrations 1 microM-100 pM (10(-6)-10(-10) M) reduced CCPR (cells/crypt/hour) 4.74 2.15-2.67 (p < 0.001), labelling index 7.28-3.74 0.01). Likewise, D2, 10 nM (10(-8) 4.74-2.74 0.05) 4.86-2.38 0.05). In polyposis 100 (10(-10) halved 8.75-4.22. Calcipotriol (10(-5) M 10(-9) produced clearcut dose response inhibition HT-29 growth. Thus, metabolites inhibit normal premalignant epithelium suppress growth
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