Chen Yao, Liu Fang-Xun, Liu Hong
Department of Traditional Chinese Medicine, Peking University International Hospital, Beijing 102206, China.
International Medical Center, Peking University International Hospital, Beijing 102206, China.
World J Gastrointest Oncol. 2021 Nov 15;13(11):1755-1765. doi: 10.4251/wjgo.v13.i11.1755.
Dietary zinc deficiency has been shown to be associated with the development of esophageal cancer in humans, but the exact mechanism of action is not known.
To observe the effects of dietary zinc deficiency on esophageal squamous cell proliferation.
Thirty C57BL/6 mice were randomly divided into three groups: A zinc-sufficient (ZS) group, zinc-deficient (ZD) group, and zinc-replenished (ZR) group. For weeks 1-10, zinc levels in the mice diets were 30.66-30.89 mg/kg in the ZS group and 0.66-0.89 mg/kg in the ZD and ZR groups. During weeks 10-12, the ZR group was switched to the ZS diet; the other two groups had no changes in their diets. Changes in body weight, serum, and esophageal tissue zinc concentrations were assessed as well as differences in the expression of proliferating cell nuclear antigen (PCNA), mitogen-activated protein kinase p38 (p38MAPK), nuclear factor kappa B (NF-κB) p105, NF-κB p65, and cyclooxygenase (COX)-2 proteins in the esophageal mucosa.
The body weight and zinc concentration in the serum and esophageal mucosa were significantly lower in the ZD and ZR groups than in the ZS group ( < 0.05). In ZD mice, there was a marked proliferation of basal cells in the esophageal mucosa, resulting in a disturbance in the arrangement of basal cells in layers 2-4, a thickening of the squamous layer, and a significant increase in the expression of the above-mentioned five proteins involved in proliferation and inflammation in the esophageal mucosa. Two weeks after switching to the ZS diet, the serum zinc concentration in the ZR group increased, and the expression of PCNA, NF-κB p105, and COX-2 decreased, but the concentration of zinc in the esophageal mucosa and the structure of the esophageal mucosa did not display any significant changes.
The ZD diet decreased the growth rate and promoted the proliferation of esophageal squamous cells in mice. The mechanism of proliferation was related to the induced overexpression of COX-2, P38, PCNA, and NF-κB (p105 and p65), and the ZR diet reduced the expression of PCNA, NF-κB p105, and COX-2, thereby reversing this process.
膳食锌缺乏已被证明与人类食管癌的发生有关，但其确切作用机制尚不清楚。
观察膳食锌缺乏对食管鳞状细胞增殖的影响。
将30只C57BL/6小鼠随机分为三组：锌充足（ZS）组、锌缺乏（ZD）组和补锌（ZR）组。在第1 - 10周，ZS组小鼠饮食中的锌含量为30.66 - 30.89mg/kg，ZD组和ZR组为0.66 - 0.89mg/kg。在第10 - 12周，ZR组改为ZS饮食；其他两组饮食不变。评估体重、血清和食管组织锌浓度的变化，以及食管黏膜中增殖细胞核抗原（PCNA）、丝裂原活化蛋白激酶p38（p38MAPK）、核因子κB（NF - κB）p105、NF - κB p65和环氧化酶（COX）-2蛋白表达的差异。
ZD组和ZR组的体重、血清及食管黏膜中的锌浓度均显著低于ZS组（<0.05）。在ZD组小鼠中，食管黏膜基底细胞显著增殖，导致2 - 4层基底细胞排列紊乱，鳞状层增厚，且食管黏膜中上述五种参与增殖和炎症的蛋白表达显著增加。改为ZS饮食两周后，ZR组血清锌浓度升高，PCNA、NF - κB p105和COX - 2的表达降低，但食管黏膜中的锌浓度和食管黏膜结构未显示任何显著变化。
ZD饮食降低了小鼠的生长速度并促进了食管鳞状细胞的增殖。增殖机制与COX - 2、P38、PCNA和NF - κB（p105和p65）的诱导过表达有关，而ZR饮食降低了PCNA、NF - κB p105和COX - 2的表达，从而逆转了这一过程。
