Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 6, 2021; 9(19): 5019-5027
Published online Jul 6, 2021. doi: 10.12998/wjcc.v9.i19.5019
SMAC exhibits anti-tumor effects in ECA109 cells by regulating expression of inhibitor of apoptosis protein family
Ning Jiang, Wei-Quan Zhang, Hong Dong, Ying-Tao Hao, Li-Ming Zhang, Lei Shan, Xiao-Dong Yang, Chuan-Liang Peng
Ning Jiang, Wei-Quan Zhang, Ying-Tao Hao, Li-Ming Zhang, Lei Shan, Xiao-Dong Yang, Chuan-Liang Peng, Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan 250100, Shandong Province, China
Hong Dong, Department of Nursing, The Second Hospital of Shandong University, Jinan 250100, Shandong Province, China
Author contributions: Jiang N and Peng CL designed the study; Zhang WQ wrote the paper; Dong H, Hao YT, and Zhang LM drafted the work and collected the data; Shan L and Yang XD collated and analyzed the data.
Institutional review board statement: The study was reviewed and approved by the Second Hospital of Shandong University Institutional Review Board.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Data sharing statement: No additional data are available.
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: Chuan-Liang Peng, MD, Chief Physician, Department of Thoracic Surgery, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Jinan 250100, Shandong Province, China. pechuliang@126.com
Received: March 4, 2021
Peer-review started: March 4, 2021
First decision: April 6, 2021
Revised: April 8, 2021
Accepted: May 19, 2021
Article in press: May 19, 2021
Published online: July 6, 2021
Processing time: 112 Days and 3.7 Hours
Abstract
BACKGROUND

The poor prognosis and rising incidence of esophageal cancer highlight the need for improved therapeutics that are essential prior to treatment. LCL161 is an SMAC (second mitochondrial activator of caspases) mimic and inhibitor of apoptosis protein (IAP) antagonist which exhibits anti-tumor effects and improves the chemical sensitivity of many cancers.

AIM

To ascertain the effects and mechanisms of the SMAC analog LCL161 on esophageal cancer cells.

METHODS

MTT assay and TUNEL assay were used to detect cell proliferation and apoptosis, respectively. Western blot analysis was used to study the molecular mechanisms of LCL161-induced death of ECA109 cells.

RESULTS

LCL161 decreased ECA109 cell proliferation in dose- and time-dependent manner and induced apoptosis of ECA109 cells in a dose-dependent manner. Also, LCL161 induced a significant decrease in the expression of the XIAP and significant increase in the expression of Caspase-3. In addition, Bax increased significantly with increasing concentrations of LCL161, and the relative expression of Bax was significantly different between groups.

CONCLUSION

These findings support the hypothesis that LCL161 can inhibit proliferation and induce apoptosis in esophageal cancer cells by regulating the expression of IAP family members, suggesting that it has potential to be an effective treatment for esophageal squamous cell carcinoma.

Keywords: SMAC; Esophageal cancer; ECA109 cell; Apoptosis protein; Inhibitor of apoptosis protein family

Core Tip: The poor prognosis and rising incidence of esophageal cancer highlight the need for improved therapeutics that are essential prior to treatment. The aim of this study was to explore the mechanisms by which SMAC (second mitochondrial activator of caspases) mimic inhibits proliferation and induce apoptosis in ECA109 esophageal cancer cells. The findings support the hypothesis that LCL161 can inhibit proliferation and induce apoptosis in esophageal cancer cells by regulating the expression of inhibitor of apoptosis proteins family members, suggesting that it has potential to be an effective treatment for esophageal squamous cell carcinoma.