vitamin-d-2 and Adenomatous-Polyposis-Coli

Eighteen patients with familial adenomatous polyposis (FAP) who had previously undergone colectomy but had upper gastrointestinal polyps were studied in a double-blind randomized crossover trial comparing sulindac with calcium and calciferol. Sulindac produced a reduction in the crypt proliferation index in the gastric epithelium of patients but did not significantly affect duodenal mucosa. Calcium with calciferol did not have any effects on crypt proliferation index in patients with FAP.

Topics: Adenomatous Polyposis Coli; Calcium; Cell Division; Common Bile Duct Neoplasms; Cross-Over Studies; Duodenal Neoplasms; Ergocalciferols; Humans; Intestinal Polyps; Prospective Studies; Stomach Neoplasms; Sulindac

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

Topics: Adenomatous Polyposis Coli; Adult; Calcitriol; Cell Division; Colonic Neoplasms; Ergocalciferols; Humans; Immunohistochemistry; Intestinal Mucosa; Rectum; Tumor Cells, Cultured; Vitamin D