Thomas M G, Brown G R, Alison M R, Williamson R C
Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Gut. 1994 Dec;35(12):1742-6. doi: 10.1136/gut.35.12.1742.
Vitamin D may protect against colorectal cancer by reducing cell proliferation and inducing differentiation. By contrast, epidermal growth factor (EGF) stimulates cell proliferation and may encourage gastrointestinal mucosal healing. This study investigated the effect of a synthetic vitamin D analogue, calcipotriol, and EGF on human rectal epithelial cell proliferation in patients with familial adenomatous polyposis (FAP). In addition, a new technique to measure the cell cycle time is described. Sigmoidoscopic biopsy specimens were obtained from 14 patients with FAP. Tissue was established in organ culture, with or without the addition of EGF (n = 8), or calcipotriol (n = 6). Proliferation was determined using (a) metaphase arrest to measure the crypt cell production rate, (b) native mitotic index, and (c) the growth fraction using PC10 antibody. EGF receptor expression was shown using a polyclonal antibody AP12E. Calcipotriol reduced crypt cell production rate by 52% from mean (SEM) 5.29 (1.18) to 2.56 (0.80) cells/crypt/hour (p < 0.01) and EGF increased crypt cell production rate by 102% from 3.62 (0.59) to 7.33 (0.90) cells/crypt/hour (p < 0.05), and this tissue expressed the EGF receptor. The growth fraction was 48.40 (4.0)%, and the native mitotic index 1.08 (0.14)%. The cell cycle time was estimated as 94.5 hours and the time for mitosis as one hour. Thus, calcipotriol and EGF have divergent effects on human rectal mucosal proliferation.
维生素D可通过减少细胞增殖和诱导分化来预防结直肠癌。相比之下，表皮生长因子（EGF）可刺激细胞增殖，并可能促进胃肠道黏膜愈合。本研究调查了合成维生素D类似物骨化三醇和EGF对家族性腺瘤性息肉病（FAP）患者直肠上皮细胞增殖的影响。此外，还描述了一种测量细胞周期时间的新技术。从14例FAP患者获取乙状结肠镜活检标本。将组织置于器官培养中，添加或不添加EGF（n = 8）或骨化三醇（n = 6）。使用以下方法测定增殖情况：（a）中期阻滞以测量隐窝细胞产生率，（b）自然有丝分裂指数，以及（c）使用PC10抗体测定生长分数。使用多克隆抗体AP12E显示EGF受体表达。骨化三醇使隐窝细胞产生率从平均（SEM）5.29（1.18）降至2.56（0.80）个细胞/隐窝/小时，降低了52%（p < 0.01），而EGF使隐窝细胞产生率从3.62（0.59）增加到7.33（0.90）个细胞/隐窝/小时，增加了102%（p < 0.05），且该组织表达EGF受体。生长分数为48.40（4.0）%，自然有丝分裂指数为1.08（0.14）%。细胞周期时间估计为94.5小时，有丝分裂时间为1小时。因此，骨化三醇和EGF对人直肠黏膜增殖有不同影响。
