Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2021; 13(11): 1755-1765
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1755
Effects of dietary zinc deficiency on esophageal squamous cell proliferation and the mechanisms involved
Yao Chen, Fang-Xun Liu, Hong Liu
Yao Chen, Department of Traditional Chinese Medicine, Peking University International Hospital, Beijing 102206, China
Fang-Xun Liu, International Medical Center, Peking University International Hospital, Beijing 102206, China
Hong Liu, Department of Gastroenterology, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China
Author contributions: Chen Y participated in experiments, analyzed data, and wrote the manuscript; Liu FX contributed to designing the study and analyzing the data with Liu H; Liu FX also participated in experiments; All authors gave their approval for the submission of the final manuscript.
Institutional review board statement: This study was approved by the Institutional Research Ethics Committee of Beijing Shijitan Hospital.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fang-Xun Liu, PhD, Attending Doctor, International Medical Center, Peking University International Hospital, No. 1 Life Park Road, Life Science Park of Zhongguancun, Changping District, Beijing 102206, China. lfx3627@163.com
Received: June 30, 2021
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
Abstract
BACKGROUND

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

AIM

To observe the effects of dietary zinc deficiency on esophageal squamous cell proliferation.

METHODS

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.

RESULTS

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

CONCLUSION

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.

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Keywords: Zinc deficiency, Esophageal cancer, Esophageal squamous cell carcinoma, Esophageal squamous cells, Cell proliferation, Inflammatory response

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.