Graduate Institute of Medical Sciences, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Proteomics. 2012 Aug;12(15-16):2584-97. doi: 10.1002/pmic.201100602.
The survivals of gastric cancer (GC) patients are associated with early diagnosis and effective treatments. Therefore, it is urgent for the discovery of early GC biomarkers and tumor-targeting therapeutics. The aim of this study was to uncover putative tissue biomarkers of GC using 2D DIGE and then apply one of these specific markers in GC treatment. We found three putative biomarkers of GC with significant differences in expression level compared to adjacent normal tissue, including glucose-regulated protein 78 (GRP78) and glutathione s-transferase pi (GSTpi) with increased expression level, and alpha-1 antitrypsin (A1AT) with reduced expression level. The overexpressed GRP78 was used as a targeted protein for guiding the drugs to tumor cells, leading to more effective treatment for GC xenografts. Our results demonstrated that the designated GRP78-binding peptide based on the sequence, WIFPWIQL, was selectively prone to recognize and bind to GC MKN45 cells in vitro, and also improve the delivery efficiency of polymeric micelles-encapsulated drugs into tumor cells and displayed better therapeutic outcome in experimental animals. This strategy of GRP78-mediated drug targeting system may bring chemotherapeutic drugs with more precise targeting to tumor cells, leading to minimize side effects on patients after chemotherapy.
胃癌（GC）患者的存活率与早期诊断和有效治疗有关。因此，迫切需要发现早期 GC 的生物标志物和肿瘤靶向治疗方法。本研究旨在使用 2D DIGE 发现 GC 的潜在组织生物标志物，然后将其中一种特定标志物应用于 GC 治疗。我们发现了三种与相邻正常组织相比表达水平有显著差异的 GC 潜在生物标志物，包括表达水平升高的葡萄糖调节蛋白 78（GRP78）和谷胱甘肽 S-转移酶 pi（GSTpi），以及表达水平降低的α-1 抗胰蛋白酶（A1AT）。过表达的 GRP78 被用作靶向蛋白，指导药物进入肿瘤细胞，从而更有效地治疗 GC 异种移植瘤。我们的结果表明，基于序列 WIFPWIQL 设计的 GRP78 结合肽在体外选择性地倾向于识别和结合 GC MKN45 细胞，并且还提高了聚合物胶束包裹药物向肿瘤细胞的递送效率，并在实验动物中显示出更好的治疗效果。这种 GRP78 介导的药物靶向系统策略可能使化疗药物更精确地靶向肿瘤细胞，从而最大限度地减少化疗后患者的副作用。
