在结肠癌细胞系SW1116中金雀异黄素通过WNT5a启动子的去甲基化提高基因的表达_王祖光

针对病种：结肠癌

发表时间：2010年11月

发表国家：希腊

登载刊物：抗癌研究

研究单位：美国伊利诺伊大学厄巴纳-尚佩恩分校食品科学和人类营养学院

研究人员：王祖光，陈宏

主要结论：在结肠癌细胞中金雀异黄素通过WNT5a启动子的去甲基化提高基因的表达，对于早期结肠癌的治疗特别有效.

ANTICANCER RESEARCH 30: 4537-4546 (2010).

Genistein Increases Gene Expression by Demethylation of WNT5a Promoter in Colon Cancer Cell Line SW1116

ZUGUANG WANG and HONG CHEN

Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, U.S.A.

Genistein (GEN), one of the soy isoflavones, exhibits protection against colon cancer. The WNT signaling pathway plays a critical role in both normal epithelial regeneration and tumorigenesis in human colon. In this study it was hypothesized that GEN regulates specific genes in the WNT signaling pathway. Colon cancer cell lines DLD-1, SW480, and SW1116 were treated with Novasoy or GEN for 4 days. mRNA levels of several WNT signaling components were analyzed by real-time PCR. Methylation-specific PCR and bisulfite genomic sequencing were used to analyze the methylation status of CpG islands. Both Novasoy and GEN inhibited cell proliferation in all three cell lines. WNT5a mRNA showed a time-dependent induction by Novasoy and GEN in DLD-1 cells but only by GEN in SW1116 cells. Meanwhile, WNT5a CpG island methylation level was decreased in SW1116 by GEN. In conclusion, GEN regulated WNT5a expression, which was accompanied by a decrease in DNA methylation level at the analyzed CpG island.

希腊《抗癌研究》2010年11月

在结肠癌细胞系SW1116中金雀异黄素通过WNT5a启动子的去甲基化提高基因的表达

王祖光，陈宏

美国伊利诺伊大学厄巴纳-尚佩恩分校食品科学和人类营养学院

金雀异黄素（GEN），是一种大豆异黄酮，可以用于结肠癌的预防与治疗。WNT 信号通路中在正常的上皮细胞再生和人类结肠肿瘤的形成中均起关键的作用。在这篇论文中，假设GEN可以调控 WNT 信号通路中的特定基因。结肠癌细胞系DLD-1，SW480， SW1116 被Novasoy 或者GEN处理了4 天。实时 PCR可以用来分析几种 WNT 信号成分的mRNA 水平。甲基化特异性 PCR 和亚硫酸氢盐基因组测序被用于分析 CpG 岛的甲基化状态。Novasoy 和GEN均抑制了三种细胞株细胞的增殖。WNT5a 的mRNA 在DLD 1中表示出由Novasoy 和GEN诱导的时间依赖性，但是在 SW1116 细胞中只有GEN诱导成功。同时GEN降低了SW1116细胞中 WNT5a的 CpG 岛的甲基化水平。总之，GEN调节了 WNT5a的表达，伴随着被分析CpG 岛的DNA 甲基化水平的降低。