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首页> 外文期刊>Oncogene >Flavopiridol reduces malignant transformation of the esophageal mucosa in p27 knockout mice
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Flavopiridol reduces malignant transformation of the esophageal mucosa in p27 knockout mice

机译：黄哌啶醇减少了P27敲除小鼠中食管粘膜的恶性转化

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The cyclin-dependent kinase (cdk) inhibitor p27 preferentially inactivates cdk complexes required for progression through the G1/S transition. Loss of p27 is associated with aggressive behavior in a variety of tumors, including Barrett's associated adenocarcinoma (BAA). We have previously shown that gastroduodenal–esophageal reflux (GDER) together with N-methyl-N-benzylnitrosamine (MBN) induces Barrett's esophagus (BE) and malignant transformation of the esophageal mucosa in mice. This process is enhanced in a p27 null background. Here, we show that chronic flavopiridol administration sharply reduced the prevalence of BE in GDER/MBN-treated p27 knockout mice when compared to animals treated with diluent only (7 vs 26%, P=0.0079). Similarly, flavopiridol reduced the prevalence of BAA (11 vs 32%, P=0.0098) and overall cancer prevalence (15 vs 60%, P<0.0001). In addition, appropriate molecular targeting by flavopiridol in tumor cells was confirmed by downregulation of cyclin D1, a known target of this pan-cdk inhibitor. The results of this study represent the experimental basis for chemoprevention with cdk inhibitors in human BE and BAA.
机译：细胞周期蛋白依赖性激酶（CDK）抑制剂P27优先通过G1 / s转变灭活进展所需的CDK络合物。 P27的丧失与各种肿瘤中的侵袭性行为有关，包括Barrett相关的腺癌（BAA）。我们之前已经表明，胃生成食管反流（Gder）与N-甲基-N-苄基硝基胺（MBN）一起诱导小鼠食管粘膜的食管（BE）和恶性转化。在P27空背景中增强了该过程。在此表明，与仅用稀释剂处理的动物（7 Vs 26 ％，P = 0.0079）相比，慢性黄哌啶酮酮急剧降低了在Gder / MBN处理的P27敲除小鼠中的流行率。类似地，黄哌啶率降低了BAA的患病率（11 Vs 32 ％，p = 0.0098）和总体癌症患病率（15 vs 60 ％，P <0.0001）。此外，通过对细胞周期蛋白D1的下调，通过对该PAN-CDK抑制剂的已知靶来证实肿瘤细胞中的黄哌啶的适当分子靶向。该研究的结果代表了用人的CDK抑制剂化学预防的实验基础。

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