{"title":"Envafolimab Inhibits the Growth of Gastric Cancer Cells with Low PD-L1 Expression through the DDX20/NF-κB/TNF-α Signaling Pathway.","authors":"Zhuanxia Dong, Zefeng Yang, Jing Ren, Feng Li, Guangyu Wang, Yusheng Wang","doi":"10.2174/0115680096314855240619181909","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The mechanism of action of envafolimab (also known as KN035), a programmed death ligand 1 (PD-L1) inhibitor, in gastric adenocarcinoma patients with low PD-L1 expression is not well understood.</p><p><strong>Aims: </strong>This study aimed to observe the efficacy of envafolimab in gastric adenocarcinoma with low PD-L1 expression and explore the underlying mechanisms.</p><p><strong>Objective: </strong>The objective of this study was to explore the underlying mechanism of envafolimab in gastric cancer with low PD-L1 expression.</p><p><strong>Method: </strong>Cytotoxicity and proliferation were evaluated by a CCK8 assay. Transwell assays were used to detect the migration and invasion ability of gastric cancer cells. The effect of envafolimab on the apoptosis of gastric cancer cells was detected by flow cytometry. The effect of envafolimab on gastric cancer cells with low PD-L1 expression was investigated via proteomics and bioinformatics analysis.</p><p><strong>Result: </strong>A total of 19 patients with advanced gastric adenocarcinoma who received envafolimab monotherapy or combination therapy were reviewed. Among them, 4 patients had low PD-L1 expression, the objective response rate (ORR) was 75% (3/4), and the disease control rate (DCR) was 100% (4/4). In vitro experiments showed that envafolimab inhibited the proliferation, invasion, and migration of gastric cancer cells with low expression of PD-L1 and induced cell apoptosis. DDX20 may be the target of envafolimab in gastric cancer cells, and it is related to the NF-κB signaling pathway. Western blot results showed that the protein expressions of DDX20, NF-κB p65, and TNF-α in gastric cancer cells were decreased after adding envafolimab. Furthermore, the DDX20 gene was silenced by small interfering RNA to further study the effect of DDX20 on PDL1 low expression in gastric cancer cells.</p><p><strong>Conclusion: </strong>This study confirmed that envafolimab could inhibit the growth of gastric cancer cells with low PD-L1 expression by down-regulating DDX20 expression and regulating the NFκB/TNF-α signaling pathway.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current cancer drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680096314855240619181909","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The mechanism of action of envafolimab (also known as KN035), a programmed death ligand 1 (PD-L1) inhibitor, in gastric adenocarcinoma patients with low PD-L1 expression is not well understood.
Aims: This study aimed to observe the efficacy of envafolimab in gastric adenocarcinoma with low PD-L1 expression and explore the underlying mechanisms.
Objective: The objective of this study was to explore the underlying mechanism of envafolimab in gastric cancer with low PD-L1 expression.
Method: Cytotoxicity and proliferation were evaluated by a CCK8 assay. Transwell assays were used to detect the migration and invasion ability of gastric cancer cells. The effect of envafolimab on the apoptosis of gastric cancer cells was detected by flow cytometry. The effect of envafolimab on gastric cancer cells with low PD-L1 expression was investigated via proteomics and bioinformatics analysis.
Result: A total of 19 patients with advanced gastric adenocarcinoma who received envafolimab monotherapy or combination therapy were reviewed. Among them, 4 patients had low PD-L1 expression, the objective response rate (ORR) was 75% (3/4), and the disease control rate (DCR) was 100% (4/4). In vitro experiments showed that envafolimab inhibited the proliferation, invasion, and migration of gastric cancer cells with low expression of PD-L1 and induced cell apoptosis. DDX20 may be the target of envafolimab in gastric cancer cells, and it is related to the NF-κB signaling pathway. Western blot results showed that the protein expressions of DDX20, NF-κB p65, and TNF-α in gastric cancer cells were decreased after adding envafolimab. Furthermore, the DDX20 gene was silenced by small interfering RNA to further study the effect of DDX20 on PDL1 low expression in gastric cancer cells.
Conclusion: This study confirmed that envafolimab could inhibit the growth of gastric cancer cells with low PD-L1 expression by down-regulating DDX20 expression and regulating the NFκB/TNF-α signaling pathway.
期刊介绍：
Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes.
Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer.
As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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