Lamprey Immune Protein Mediates Apoptosis of Lung Cancer Cells Via the Endoplasmic Reticulum Stress Signaling Pathway.

Lamprey Immune Protein Mediates Apoptosis of Lung Cancer Cells Via the Endoplasmic Reticulum Stress Signaling Pathway.
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七鳃鳗免疫蛋白通过内质网应激信号通路介导肺癌细胞凋亡

DOI:
10.3389/fonc.2021.663600
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发表时间:
2021
影响因子:
4.7
通讯作者:
Li Q
Li Q
中科院分区:
医学3区
文献类型:
--
作者:
Song X;Xu X;Lu J;Chi X;Pang Y;Li Q

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七鳃鳗免疫蛋白(LIP)是一种来源于日本七鳃鳗的新型蛋白质,具有高效的杀肿瘤作用,对健康细胞无损伤。我们的研究旨在确定LIP抑制肺癌细胞的机制,从而描绘潜在的创新治疗策略。采用免疫印迹法和免疫组化法检测LIP在肺癌细胞中的表达。功能分析,如高内容成像,三维结构照明显微镜(3D-SIM)成像,流式细胞术,共聚焦激光扫描显微镜,进行检查的增殖和肺癌细胞凋亡。使用体内成像系统进行肿瘤异种移植物测定。我们观察到LIP通过破坏细胞器如微管、线粒体和内质网(ER)诱导某些肺癌细胞膜的分解,此外还导致细胞质渗漏,使得维持稳态变得困难。我们还证明,LIP激活ER应激途径,其通过产生活性氧(ROS)介导肺癌细胞凋亡。此外,注射LIP显著延缓裸鼠肿瘤的生长速率。总之,这些数据揭示了LIP通过控制ER应激信号通路在调节肺癌细胞凋亡中的作用,从而揭示了其在肺癌治疗中的可能应用。
Lamprey immune protein (LIP), a novel protein derived from the Lampetra japonica, has been shown to exert efficient tumoricidal actions without concomitant damage to healthy cells. Our study aimed to ascertain the mechanisms by which LIP inhibits lung cancer cells, thus delineating potential innovative therapeutic strategies. LIP expression in lung cancer cells was evaluated by western blotting and immunohistochemistry. Functional assays, such as high-content imaging, 3D-structured illumination microscopy (3D-SIM) imaging, flow cytometry, and confocal laser scanning microscopy, were performed to examine the proliferation and lung cancer cell apoptosis. Tumor xenograft assays were performed using an in vivo imaging system. We observed that LIP induces the decomposition of certain lung cancer cell membranes by destroying organelles such as the microtubules, mitochondria, and endoplasmic reticulum (ER), in addition to causing leakage of cytoplasm, making the maintenance of homeostasis difficult. We also demonstrated that LIP activates the ER stress pathway, which mediates lung cancer cell apoptosis by producing reactive oxygen species (ROS). In addition, injection of LIP significantly retarded the tumor growth rate in nude mice. Taken together, these data revealed a role of LIP in the regulation of lung cancer cell apoptosis via control of the ER stress signaling pathway, thus revealing its possible application in lung cancer treatment.
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