Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2024; 30(4): 367-380
Published online Jan 28, 2024. doi: 10.3748/wjg.v30.i4.367
Amlodipine inhibits the proliferation and migration of esophageal carcinoma cells through the induction of endoplasmic reticulum stress
Yan-Min Chen, Wen-Qian Yang, Cheng-Wei Gu, Ying-Ying Fan, Yu-Zhen Liu, Bao-Sheng Zhao
Yan-Min Chen, Wen-Qian Yang, Cheng-Wei Gu, Yu-Zhen Liu, Bao-Sheng Zhao, Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China
Yan-Min Chen, Department of Oncology, The Affiliated Hospital, Henan Polytechnic University, Jiaozuo 454000, Henan Province, China
Wen-Qian Yang, Yu-Zhen Liu, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China
Ying-Ying Fan, Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China
Author contributions: Chen YM, Liu YZ, and Zhao BS made substantial contributions to conception and design of the study; Chen YM and Yang WQ conducted the experiments, acquired and analyzed data; Chen YM, Yang WQ, Liu YZ, and Zhao BS interpreted the data; Gu CW and Fan YY were responsible for clinical sample collection; Chen YM and Liu YZ wrote the manuscript drift; Liu YZ and Zhao BS revised the manuscript; and all authors approved the final version of the manuscript.
Supported by the Key Medical Scientific and Technological Project of Henan Province, No. SBGJ202102188; Henan Provincial Medical Science and Technology Project, No. LHGJ20221012; and the Key Project of Science and Technology of Xinxiang, No. GG2020027.
Institutional review board statement: This study was reviewed and approved by the First Affiliated Hospital of Xinxiang Medical University Institutional Review Board (Approval No. EC-023-487).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the First Affiliated Hospital of Xinxiang Medical University Institutional Review Board (Approval No. EC-023-488).
Conflict-of-interest statement: The authors declare that no conflict of interest exists in this study.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bao-Sheng Zhao, BMed, Chief Physician, Professor, Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, No. 88 Jiankang Road, Weihui 453100, Henan Province, China. drbszhao@xxmu.edu.cn
Received: December 12, 2023
Peer-review started: December 12, 2023
First decision: December 19, 2023
Revised: December 21, 2023
Accepted: January 3, 2024
Article in press: January 3, 2024
Published online: January 28, 2024
Processing time: 45 Days and 4.1 Hours
ARTICLE HIGHLIGHTS
Research background

Esophageal cancer (EC) is the sixth most common tumor worldwide and has a poor prognosis. Although L-type calcium channel blockers have demonstrated efficacy in inhibiting the occurrence and development of various tumors, their impact on EC remains unclear.

Research motivation

Patients with EC have a poor prognosis owing to a lack of effective treatments and prognostic indicators. This study aimed to explore a novel approach for treating EC and improving patient survival rates.

Research objectives

To elucidate the mechanism by which the L-type calcium channel blocker, amlodipine, inhibits the proliferation and migration of EC cells, thereby offering a potential new avenue for the treatment of EC.

Research methods

Western blot analysis was used to assess the expression of relevant proteins. Cell migration was evaluated using Transwell assays and apoptosis was measured using flow cytometry. The endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid was used to prevent ER stress. Transduction of EC cells with GFP-RFP-LC3 adenovirus confirmed that amlodipine-mediated ER stress functions through downstream autophagy. In addition, a murine xenograft model constructed using Eca109 cells was used to validate the anti-tumor effects of amlodipine in vivo.

Research results

This study revealed that the Cav1.3 level in EC tissues was higher than that in adjacent tissues. The L-type calcium channel blocker, amlodipine, inhibits the proliferation and migration of EC cells while promoting apoptosis. Mechanistic investigations have indicated that these effects are associated with the induction of cellular ER stress. Further studies using GFP-RFP-LC3 adenovirus-transfected cells treated with amlodipine demonstrated that autophagy, mediated by ER stress, played a protective role in this process. In addition, amlodipine inhibited EC cell growth and presented an antitumor effect in vivo.

Research conclusions

L-type calcium channels are highly expressed in EC tissues. Both in vivo and in vitro experiments revealed that amlodipine inhibited the proliferation and migration of EC cells through ER stress.

Research perspectives

The expression levels of L-type calcium channels in EC may serve as an index of prognosis, and the combination of amlodipine with autophagy inhibitors holds promise as a novel treatment approach. Future endeavors should involve large-sample multicenter clinical studies to further validate its reliability.