Abstract：
Granzyme B (GZMB), a critical member of the Gr gene family, is known to play an essential role in diverse physiological and pathological processes such as inflammation, acute and chronic inflammatory diseases, and cancer progression. In this study, we delve deeper into the role of GZMB within the context of gastric cancer (GC) to examine its expression patterns and functional implications. To accomplish this, we applied a combination of quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry techniques. These methodologies allowed us to accurately gauge GZMB expression levels in GC tissues and investigate their correlation with various clinical-pathological variables. Our secondary focus was to discern the regulatory influence of GZMB on GC cell biology. We used an array of assays including cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2\'-deoxyuridine, and migration assays. The effect of GZMB on gastric cancer progression was further validated through a subcutaneous xenograft mouse model. Our findings underscored that GZMB mRNA and protein levels were upregulated in GC tissues, a feature that showed a significant correlation with GC staging. We also discovered that a decrease in GZMB expression via knockdown experiments suppressed the proliferation and migration capabilities of GC cells. This effect was manifested through diminished expression levels of epithelial-mesenchymal transition (EMT) markers. In stark contrast, the overexpression of GZMB through plasmid transfection appeared to enhance the proliferation and migration abilities of GC cells. This was coupled with an upregulation in EMT expression. Our study concludes by emphasizing that GZMB promotes the growth, migration, and EMT processes in gastric cancer. In vitro, cell-based experiments and in vivo xenograft mouse models confirm this. Our findings provide a more comprehensive understanding of GZMB\'s role in gastric cancer pathogenesis, potentially opening doors for novel therapeutic strategies targeting this molecular pathway.
摘要：
颗粒酶B（GZMB），Gr基因家族的重要成员,众所周知，在炎症等多种生理和病理过程中起着至关重要的作用，急性和慢性炎症性疾病，和癌症进展。在这项研究中,我们深入研究了GZMB在胃癌（GC）中的作用，以检查其表达模式和功能意义。要做到这一点，我们应用了定量实时聚合酶链反应的组合，西方印迹,和免疫组织化学技术。这些方法使我们能够准确地测量GC组织中的GZMB表达水平，并研究其与各种临床病理变量的相关性。我们的次要重点是辨别GZMB对GC细胞生物学的调节影响。我们使用了一系列的检测方法，包括细胞计数试剂盒-8（CCK-8），菌落形成,5-乙炔基-2'-脱氧尿苷，和迁移测定。通过皮下异种移植小鼠模型进一步验证了GZMB对胃癌进展的影响。我们的发现强调GZMBmRNA和蛋白质水平在GC组织中上调，与GC分期有显著相关性的特征。我们还发现，通过敲低实验降低GZMB表达抑制了GC细胞的增殖和迁移能力。这种作用通过上皮-间质转化(EMT)标记物的表达水平降低来证明。与之形成鲜明对比的是,通过质粒转染GZMB的过表达似乎增强了GC细胞的增殖和迁移能力。这与EMT表达的上调相关。我们的研究结论是强调GZMB促进了增长，迁移,和胃癌的EMT过程。体外，基于细胞的实验和体内异种移植小鼠模型证实了这一点。我们的发现为GZMB在胃癌发病机制中的作用提供了更全面的理解。可能为针对这种分子途径的新型治疗策略打开大门。
