Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1755
Peer-review started: June 30, 2021
First decision: July 18, 2021
Revised: July 30, 2021
Accepted: September 29, 2021
Article in press: September 29, 2021
Published online: November 15, 2021
Processing time: 135 Days and 1.4 Hours
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 (P < 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.
Core Tip: 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. The aim of this study was to observe the effects of dietary zinc deficiency on esophageal squamous cell proliferation. In addition, we investigated the pathway of zinc deficiency-induced esophageal squamous cell proliferation by detecting the expression of five predictive biomarkers. The results of the study showed that zinc-deficient diet decreased the growth rate and promoted the proliferation of esophageal epithelial squamous cells in mice. The mechanism was related to the induced overexpression of cyclooxygenase-2, P38, proliferating cell nuclear antigen, and nuclear factor kappa B (p105 and p65), and zinc replenishment reduced the expression of proliferating cell nuclear antigen, nuclear factor kappa B p105, and cyclooxygenase-2, thereby reversing this process.