Envafolimab Inhibits the Growth of Gastric Cancer Cells with Low PD-L1 Expression through the DDX20/NF-κB/TNF-α Signaling Pathway.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-07-15 DOI:10.2174/0115680096314855240619181909

Zhuanxia Dong, Zefeng Yang, Jing Ren, Feng Li, Guangyu Wang, Yusheng Wang

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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.

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恩伐利单抗通过DDX20/NF-κB/TNF-α信号通路抑制PD-L1低表达胃癌细胞的生长

背景：恩伐单抗（又称KN035）是一种程序性死亡配体1（PD-L1）抑制剂，其在PD-L1低表达的胃腺癌患者中的作用机制尚不十分清楚：本研究旨在探讨恩伐利单抗在PD-L1低表达胃腺癌中的作用机制：方法：通过CCK8试验评估细胞毒性和增殖。方法：用 CCK8 试验评估细胞毒性和增殖，用 Transwell 试验检测胃癌细胞的迁移和侵袭能力。通过流式细胞术检测恩伐单抗对胃癌细胞凋亡的影响。通过蛋白质组学和生物信息学分析研究了恩伐利单抗对PD-L1低表达胃癌细胞的影响：结果：共回顾了19例接受恩伐利单抗单药或联合治疗的晚期胃腺癌患者。其中，4例患者PD-L1低表达，客观反应率（ORR）为75%（3/4），疾病控制率（DCR）为100%（4/4）。体外实验显示，恩伐利单抗可抑制PD-L1低表达胃癌细胞的增殖、侵袭和迁移，并诱导细胞凋亡。DDX20可能是恩伐利单抗在胃癌细胞中的靶点，它与NF-κB信号通路有关。Western blot结果显示，加入恩伐利单抗后，胃癌细胞中DDX20、NF-κB p65和TNF-α的蛋白表达量均有所下降。此外，通过小干扰RNA沉默DDX20基因，进一步研究了DDX20对胃癌细胞中PDL1低表达的影响：本研究证实，恩伐利单抗可通过下调DDX20的表达和调节NFκB/TNF-α信号通路来抑制PD-L1低表达胃癌细胞的生长。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464