Song Xiaoping, Xu Xiangting, Lu Jiali, Chi Xiaoyuan, Pang Yue, Li Qingwei
College of Life Science, Liaoning Normal University, Dalian, China.
Lamprey Research Center, Liaoning Normal University, Dalian, China.
Front Oncol. 2021 Jul 7;11:663600. doi: 10.3389/fonc.2021.663600. eCollection 2021.
Lamprey immune protein (LIP), a novel protein derived from the , 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 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 control of the ER stress signaling pathway, thus revealing its possible application in lung cancer treatment.
七鳃鳗免疫蛋白（LIP）是一种源自七鳃鳗的新型蛋白质，已被证明能发挥有效的杀瘤作用，同时不会对健康细胞造成损害。我们的研究旨在确定LIP抑制肺癌细胞的机制，从而描绘出潜在的创新治疗策略。通过蛋白质印迹法和免疫组织化学评估肺癌细胞中LIP的表达。进行了诸如高内涵成像、三维结构光照显微镜（3D-SIM）成像、流式细胞术和共聚焦激光扫描显微镜等功能测定，以检测肺癌细胞的增殖和凋亡。使用成像系统进行肿瘤异种移植试验。我们观察到，LIP除了导致细胞质泄漏，使细胞内稳态难以维持外，还通过破坏微管、线粒体和内质网（ER）等细胞器诱导某些肺癌细胞膜的分解。我们还证明，LIP激活内质网应激途径，该途径通过产生活性氧（ROS）介导肺癌细胞凋亡。此外，注射LIP显著延缓了裸鼠的肿瘤生长速度。综上所述，这些数据揭示了LIP在调节肺癌细胞凋亡和控制内质网应激信号通路中的作用，从而揭示了其在肺癌治疗中的可能应用。
