Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial
Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial
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DOI：
10.1136/gut.2008.162933
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发表时间：
2009-03-01
期刊：
影响因子：
24.5
通讯作者：
Mathers, J. C.
中科院分区：
文献类型：
--
作者：
Dronamraju, S. S.;Coxhead, J. M.;Mathers, J. C.
目的：研究口服抗性淀粉(RS)对结直肠癌(CRC)患者肿瘤细胞和结肠粘膜细胞动力学及基因表达的影响，并探讨其在结肠癌预防中的作用。方法：65例大肠癌患者随机分为RS组和普通淀粉组(OS)。结果：RS组结肠隐窝上半部有丝分裂细胞比例(3.11.5)明显低于OS组(13.73.2)(p=0.028)。然而，RS治疗对隐窝大小和肿瘤细胞增殖指数没有影响。与肉眼正常粘膜相比，肿瘤组织中CDK4的表达显著上调(P<0.001)，GADD45A的表达显著下调(P<0.05)。RS治疗后，CDK4在肿瘤中的表达(0.88(0.15))是OS组(0.37(0.16))的两倍(p=0.02)。在癌症存在的情况下，GADD45A的表达在RS治疗后显著上调(p=0.048)，与OS治疗(0.56(0.3))相比，RS治疗(1.41(0.26))显著上调。结论：结肠隐窝上部的细胞增殖是癌前病变的标志，补充RS对其抑制作用与该食物成分的抗肿瘤作用相一致。关键细胞周期调控基因的差异表达可能有助于RS抗肿瘤作用的分子机制。试验注册号：ISRCTN93586244。
Objective: This study investigated the effects of oral supplementation of resistant starch (RS) on tumour cell and colonic mucosal cell kinetics and on gene expression in patients with colorectal cancer (CRC), and its potential role in colon cancer prevention.Methods: 65 patients with CRC were randomised to treatment with RS or ordinary starch (OS) and were given starch treatment for up to 4 weeks. Pretreatment and post-treatment biopsies were obtained from the tumour and colonic mucosa, and the effects of the starch treatment on cell proliferation and expression of the cell cycle regulatory genes CDK4 (cyclin-dependent kinase 4) and GADD45A (growth arrest and DNA damage-inducible, alpha) were investigated.Results: The proportion of mitotic cells in the top half of the colonic crypt was significantly lower following RS treatment (3.1 (1.5), mean (SEM)) as compared with OS treatment (13.7 (3.2)) (p = 0.028). However, there was no effect of RS treatment on crypt dimensions and tumour cell proliferation index. There was significant upregulation in expression of CDK4 (p < 0.01) and downregulation in expression of GADD45A (p < 0.001) in the tumour tissue when compared with macroscopically normal mucosa. Following RS treatment, CDK4 expression in tumours (0.88 (0.15)) was twofold higher than that in the OS group (0.37 (0.16)) (p = 0.02). The expression of GADD45A, which was downregulated in the presence of cancer, was significantly upregulated (p = 0.048) following RS treatment (1.41 (0.26)) as compared with OS treatment (0.56 (0.3)). However, there were no significant differences in the expression of these genes in the normal mucosa following starch treatment.Conclusions: Cell proliferation in the upper part of colonic crypts is a premalignant marker and its reduction by RS supplementation is consistent with an antineoplastic action of this food component. Differential expression of the key cell cycle regulatory genes may contribute to the molecular mechanisms underlying these antineoplastic effects of RS.Trial registration number: ISRCTN93586244.