Dendrobine Suppresses Tumor Growth by Regulating the PD-1/PD-L1 Checkpoint Pathway in Lung Cancer.

IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2024-09-18 DOI:10.2174/0115680096305416240820040314

Linmao Li, Jiejin Nong, Jingui Li, Lini Fang, Meini Pan, Haixian Qiu, Shiqing Huang, Yepeng Li, Meijuan Wei, Haiying Yin

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引用次数: 0

Abstract

Background: Dendrobine is a bioactive alkaloid isolated from Dendrobium nobile. Studies have evaluated the anti-tumor effect of dendrobine in cancers, including lung cancer. However, the mechanism of dendrobine inhibiting tumors requires further study.

Methods: Bioinformatics was performed to screen the potential targets of dendrobine. The in-tersection of dendrobine and lung cancer targets was performed for KEGG analysis. CCK-8 was used to detect cell viability after dendrobine treatment. A xenograft mouse model was es-tablished to explore the effect of dendrobine on lung cancer. The percentages of PD-L1+, CD4+, CD8+, CD11b+, CD25+FOXP3+ cells, the expression of Ki-67 and caspase-3, the ex-pression of pathway-related proteins, the levels of IL-2, IFN-γ, and TGF-β, and the changes of indicators of liver and renal function were measured.

Results: Dendrobine regulated the PD1/PD-L1 checkpoint signaling pathway and affected the occurrence and development of lung cancer. Dendrobine decreased the cell viability of lung cancer. Dendrobine and anti-PD-L1 decreased tumor growth, increased caspase-3 expression, and reduced Ki-67 expression in tumor tissues. Dendrobine and anti-PD-L1 suppressed pro-tein expression of PD-L1, p-JAK1/JAK1, and p-JAK2/JAK2 in tumor tissues. Greatly, den-drobine and anti-PD-L1 decreased the percentages of PD-L1+, CD11b+, and CD25+FOXP3+ cells, increased the percentages of CD4+ and CD8+cells, and enhanced the levels of IL-2, IFN-γ, and TGF-β in tumor tissues. Dendrobine demonstrated no hepatorenal toxicity to the tumor mice. The combination of dendrobine and anti-PD-L1 greatly strengthened the effects of dendrobine on tumors.

Conclusion: Dendrobine inhibited tumor immune escape by suppressing the PD-1/PD-L1 checkpoint pathway, thus restricting tumor growth of lung cancer.

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石斛碱通过调节肺癌中的 PD-1/PD-L1 检查点通路抑制肿瘤生长

背景：石斛碱是从金钗石斛中分离出来的一种生物活性生物碱。研究评估了石斛碱对癌症（包括肺癌）的抗肿瘤作用。然而，石斛碱抑制肿瘤的机制还需要进一步研究：方法：采用生物信息学方法筛选石斛碱的潜在靶点。方法：采用生物信息学方法筛选石斛碱的潜在靶点，并对石斛碱与肺癌靶点的内切关系进行 KEGG 分析。用CCK-8检测石斛碱处理后的细胞活力。建立异种移植小鼠模型，探讨石斛碱对肺癌的影响。结果表明：石斛碱对PD-L1+、CD4+、CD8+、CD11b+、CD25+FOXP3+细胞的百分比、Ki-67和caspase-3的表达、通路相关蛋白的表达、IL-2、IFN-γ和TGF-β的水平以及肝肾功能指标的变化均有调节作用：结果：石斛碱调节了PD1/PD-L1检查点信号通路，影响了肺癌的发生和发展。结果：石斛碱调控PD1/PD-L1检查点信号通路，影响肺癌的发生和发展。石斛碱和抗PD-L1能降低肿瘤组织中的肿瘤生长、增加caspase-3的表达和减少Ki-67的表达。石斛碱和抗 PD-L1 可抑制肿瘤组织中 PD-L1、p-JAK1/JAK1 和 p-JAK2/JAK2 的蛋白表达。地屈孕酮和抗-PD-L1可显著降低肿瘤组织中PD-L1+、CD11b+和CD25+FOXP3+细胞的百分比，增加CD4+和CD8+细胞的百分比，并提高IL-2、IFN-γ和TGF-β的水平。石斛碱对肿瘤小鼠没有肝肾毒性。石斛碱与抗PD-L1联用可大大增强石斛碱对肿瘤的作用：结论：石斛碱通过抑制PD-1/PD-L1检查点通路抑制肿瘤免疫逃逸，从而限制肺癌肿瘤的生长。

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

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

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.