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通过调节肿瘤相关巨噬细胞中 IRE1α/XBP-1 信号通路研究 PD-L1 对非小细胞肺癌转移增殖的调控机制。

Mechanistic study of PD-L1 regulation of metastatic proliferation in non-small cell lung cancer through modulation of IRE1α/XBP-1 signaling pathway in tumor-associated macrophages.

机构信息

Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Aging (Albany NY). 2024 Aug 24;16(16):12063-12072. doi: 10.18632/aging.206082.

Abstract

OBJECTIVE

To explore the related research of PD-L1 in IRE1α/XBP-1 signaling pathway on non-small cell lung cancer.

METHODS

The tumor model of mice was established and divided into four groups; after successful modeling, the tumor tissue of mice was removed for subsequent experiments; the bought THP-1 cells were grouped into four different groups, a control group, nivolumab intervention group, IRE1α inhibition group, and nivolumab intervention + IRE1α inhibition group; after co-culture of the four groups of THP-1 cells with A549, THP-1 cell protein levels in the four groups were analyzed using Western blot; A549 cell migration, invasion and proliferation were assessed using the scratch assay, Transwell method, monoclonal experiment and CCK-8 method.

RESULTS

studies indicated that the stimulation of nivolumab could strongly check the progress of NSCLC (non-small cell lung); two groups treated with 4 μ8c showed obvious effects on check point of NSCLC; experiments including Western-blot experiment, Scratch experiment, Transwell method, Monoclonal experiment and CCK-8 experiment suggest that nivolumab could inhibit migration, invasion and proliferation of NSCLC tumor cells and it.

CONCLUSION

PD-L1 is capable of controlling metastatic and proliferative potential of NSCLC by the way of the modification of IRE1α/XBP-1 signaling in tumor-associated macrophages.

摘要

目的

探索 PD-L1 在 IRE1α/XBP-1 信号通路对非小细胞肺癌中的相关研究。

方法

建立小鼠肿瘤模型并分为四组;成功建模后,取出小鼠的肿瘤组织用于后续实验;购买 THP-1 细胞并分为四组,即对照组、nivolumab 干预组、IRE1α 抑制组和 nivolumab 干预+IRE1α 抑制组;将四组 THP-1 细胞与 A549 共培养后,使用 Western blot 分析四组 THP-1 细胞的蛋白水平;通过划痕实验、Transwell 法、克隆实验和 CCK-8 法评估 A549 细胞的迁移、侵袭和增殖。

结果

研究表明,nivolumab 的刺激可强烈抑制 NSCLC(非小细胞肺癌)的进展;用 4μ8c 处理的两组对 NSCLC 的检查点有明显作用;Western blot 实验、划痕实验、Transwell 法、克隆实验和 CCK-8 实验表明,nivolumab 可抑制 NSCLC 肿瘤细胞的迁移、侵袭和增殖。

结论

PD-L1 通过肿瘤相关巨噬细胞中 IRE1α/XBP-1 信号通路的修饰,能够控制 NSCLC 的转移和增殖潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c67/11386930/255f66347c98/aging-16-206082-g001.jpg

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