Birtekocak Fatih, Demirbolat Gulen Melike, Cevik Ozge
Department of Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin, Turkey.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Biruni University, Istanbul, Turkey.
Iran J Pharm Res. 2021 Spring;20(2):45-56. doi: 10.22037/ijpr.2020.112069.13514.
Colon cancer is one of the most prominent causes of cancer-related morbidity and mortality and curable if detected in the early stages. TNF-related apoptosis-inducing ligand (TRAIL) is a therapeutic protein and has a potential anti-cancer activity that is widely used for the treatment of several cancers. In this study, we aimed to develop a silver nanoparticle system conjugated with TRAIL and coated with PEG (AgCTP NPs) to improve the therapeutic effects of colon cancer. AgCTP NPs were characterized by UV spectrum, FTIR and zetasizer. Cytotoxicity, hemolysis assay and apoptotic effects of nanoparticles were investigated using a colon cancer cell line (HT-29) . Treatment with AgCTP NPs effectively inhibited proliferation and colony formation of HT-29 cells. The apoptotic effects of nanoparticles on HT-29 cells were determined as Bax, Bcl-2, PARP and clv-PARP protein expression levels using Western blot. Apoptotic proteins were upregulated by AgCTP NPs. In this study, we demonstrated that AgCTP NPs had an anti-cancer effect by activating cell death. Thus, we have confirmed that silver nanoparticles can be selected as a good carrier for TRAIL therapeutic proteins that can be used to treat colon cancer.
结肠癌是癌症相关发病和死亡的最主要原因之一，若在早期阶段被发现则可治愈。肿瘤坏死因子相关凋亡诱导配体（TRAIL）是一种治疗性蛋白质，具有潜在的抗癌活性，被广泛用于多种癌症的治疗。在本研究中，我们旨在开发一种与TRAIL共轭并包覆聚乙二醇的银纳米颗粒系统（AgCTP NPs），以提高结肠癌的治疗效果。通过紫外光谱、傅里叶变换红外光谱和zeta电位仪对AgCTP NPs进行了表征。使用结肠癌细胞系（HT-29）研究了纳米颗粒的细胞毒性、溶血试验和凋亡作用。用AgCTP NPs处理可有效抑制HT-29细胞的增殖和集落形成。通过蛋白质免疫印迹法测定纳米颗粒对HT-29细胞的凋亡作用，以检测Bax、Bcl-2、PARP和裂解的PARP蛋白表达水平。AgCTP NPs使凋亡蛋白上调。在本研究中，我们证明了AgCTP NPs通过激活细胞死亡发挥抗癌作用。因此，我们证实银纳米颗粒可被选为TRAIL治疗性蛋白质的良好载体，用于治疗结肠癌。
