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2000
Volume 25, Issue 6
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

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.

Objectives

The objective of this study was to explore the underlying mechanism of envafolimab in gastric cancer with low PD-L1 expression.

Methods

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 proteomics and bioinformatics analysis.

Results

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). 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 PD-L1 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 NF-κB/TNF-α signaling pathway.

© 2025 Bentham Science Publishers
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/content/journals/ccdt/10.2174/0115680096314855240619181909
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Envafolimab Inhibits the Growth of Gastric Cancer Cells with Low PD-L1 Expression through the DDX20/NF-κB/TNF-α Signaling Pathway
Curr. Cancer Drug Targets< 25, 648 (2025); https://doi.org/10.2174/0115680096314855240619181909
/content/journals/ccdt/10.2174/0115680096314855240619181909
/content/journals/ccdt/10.2174/0115680096314855240619181909
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  • Article Type:     Research Article
Keyword(s): DDX20; Envafolimab (KN035); gastric cancer; NF-κB; PD-L1; PD-L1 inhibitor

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