Potential ‘anti-cancer’ effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cells

Abstract Background Esketamine, an N-methyl-D-aspartate receptor antagonist, is commonly used for anesthesia and analgesia clinically. It was reported to negatively regulate cell proliferation, metastasis and apoptosis in cancer cells, including lung cancer and pancreatic cancer. However, its impact...

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Main Authors: Chao Li, Jingpu Shi, Sisi Wei, Huiqun Jia
Format: Article
Language:English
Published: BMC 2023-11-01
Series:European Journal of Medical Research
Subjects:
Online Access:https://doi.org/10.1186/s40001-023-01511-x
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author Chao Li
Jingpu Shi
Sisi Wei
Huiqun Jia
author_facet Chao Li
Jingpu Shi
Sisi Wei
Huiqun Jia
author_sort Chao Li
collection DOAJ
description Abstract Background Esketamine, an N-methyl-D-aspartate receptor antagonist, is commonly used for anesthesia and analgesia clinically. It was reported to negatively regulate cell proliferation, metastasis and apoptosis in cancer cells, including lung cancer and pancreatic cancer. However, its impact on esophageal squamous cell carcinoma (ESCC) malignance and underlying mechanism remain elusive. This study was aimed to investigate the antitumor effects of esketamine on ESCC in vitro. Methods ESCC cell lines (KYSE-30 and KYSE-150) were cultured and treated with different concentrations (0.1, 0.2, 0.4, 0.8, 1, 2 mM) of esketamine. Their proliferation, apoptosis, migration and invasion were assessed with various assays. Furthermore, mass spectrometry-based proteomic analysis and GO/KEGG enrichment analysis were applied to characterize the differentially expressed proteins (DEPs) with or without esketamine treatment. Some key proteins identified from proteomic analysis were further validated with Western blotting and bioinformatics analysis. Results Esketamine significantly inhibited the proliferation, migration, invasion and promoted apoptosis of the both types of cell lines in a dose- and time-dependent manner. A total of 321 common DEPs, including 97 upregulated and 224 downregulated proteins, were found with HPLC–MS analyses. GO/KEGG enrichment analysis suggested that esketamine affected cell population proliferation, GTPase activity and Apelin signaling pathway. The ERCC6L, AHR and KIF2C protein expression was significantly downregulated in these ESCC cells treated with esketamine compared to the controls and their changes were associated with the suppressive effects of esketamine on ESCC through bioinformatics analysis. Conclusions Our work demonstrated that esketamine has potential anti-ESCC properties in vitro but subjected to further in vivo and clinical study.
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spelling doaj.art-1d125071935c442d90e3aa9dfbc5f9492023-11-19T12:47:10ZengBMCEuropean Journal of Medical Research2047-783X2023-11-0128111310.1186/s40001-023-01511-xPotential ‘anti-cancer’ effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cellsChao Li0Jingpu Shi1Sisi Wei2Huiqun Jia3Department of Anesthesiology, The Fourth Hospital of Hebei Medical UniversityDepartment of Anesthesiology, The Fourth Hospital of Hebei Medical UniversityScientific Research Center, The Fourth Hospital of Hebei Medical UniversityDepartment of Anesthesiology, The Fourth Hospital of Hebei Medical UniversityAbstract Background Esketamine, an N-methyl-D-aspartate receptor antagonist, is commonly used for anesthesia and analgesia clinically. It was reported to negatively regulate cell proliferation, metastasis and apoptosis in cancer cells, including lung cancer and pancreatic cancer. However, its impact on esophageal squamous cell carcinoma (ESCC) malignance and underlying mechanism remain elusive. This study was aimed to investigate the antitumor effects of esketamine on ESCC in vitro. Methods ESCC cell lines (KYSE-30 and KYSE-150) were cultured and treated with different concentrations (0.1, 0.2, 0.4, 0.8, 1, 2 mM) of esketamine. Their proliferation, apoptosis, migration and invasion were assessed with various assays. Furthermore, mass spectrometry-based proteomic analysis and GO/KEGG enrichment analysis were applied to characterize the differentially expressed proteins (DEPs) with or without esketamine treatment. Some key proteins identified from proteomic analysis were further validated with Western blotting and bioinformatics analysis. Results Esketamine significantly inhibited the proliferation, migration, invasion and promoted apoptosis of the both types of cell lines in a dose- and time-dependent manner. A total of 321 common DEPs, including 97 upregulated and 224 downregulated proteins, were found with HPLC–MS analyses. GO/KEGG enrichment analysis suggested that esketamine affected cell population proliferation, GTPase activity and Apelin signaling pathway. The ERCC6L, AHR and KIF2C protein expression was significantly downregulated in these ESCC cells treated with esketamine compared to the controls and their changes were associated with the suppressive effects of esketamine on ESCC through bioinformatics analysis. Conclusions Our work demonstrated that esketamine has potential anti-ESCC properties in vitro but subjected to further in vivo and clinical study.https://doi.org/10.1186/s40001-023-01511-xEsketamineEsophageal squamous cell carcinomaProliferationApoptosisProteomics
spellingShingle Chao Li
Jingpu Shi
Sisi Wei
Huiqun Jia
Potential ‘anti-cancer’ effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cells
European Journal of Medical Research
Esketamine
Esophageal squamous cell carcinoma
Proliferation
Apoptosis
Proteomics
title Potential ‘anti-cancer’ effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cells
title_full Potential ‘anti-cancer’ effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cells
title_fullStr Potential ‘anti-cancer’ effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cells
title_full_unstemmed Potential ‘anti-cancer’ effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cells
title_short Potential ‘anti-cancer’ effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cells
title_sort potential anti cancer effects of esketamine on proliferation apoptosis migration and invasion in esophageal squamous carcinoma cells
topic Esketamine
Esophageal squamous cell carcinoma
Proliferation
Apoptosis
Proteomics
url https://doi.org/10.1186/s40001-023-01511-x
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AT sisiwei potentialanticancereffectsofesketamineonproliferationapoptosismigrationandinvasioninesophagealsquamouscarcinomacells
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