Mohamed Mohamed R, Osman Soheir A, Hassan Asmaa A, Raafat Amany I, Refaat Mahmoud M, Fathy Shadia A
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Radiation Biology Department, National Centre for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Int J Immunopathol Pharmacol. 2024 Jan-Dec;38:3946320241263352. doi: 10.1177/03946320241263352.
Gemcitabine (GEM) is a deoxycytidine analog chemotherapeutic drug widely used to treat many cancers. Silver nanoparticles (AgNPs) are important nanomaterials used to treat many diseases. Using gamma radiation in nanoparticle preparation is a new eco-friendly method. This study aims to evaluate the efficiency of co-treating gemcitabine and silver nanoparticles in treating hepatocellular carcinoma. The AgNPs were characterized using UV-visible spectroscopy, XRD, TEM, and EDX. The MTT cytotoxicity in vitro assay of gemcitabine, doxorubicin, and cyclophosphamide was assessed against Wi38 normal fibroblast and HepG2 HCC cell lines. After HCC development, rats received (10 µg/g b.wt.) of AgNPs three times a week for 4 weeks and/or GEM (5 mg/kg b.wt.) twice weekly for 4 weeks. Liver function enzymes were investigated. Cytochrome P450 and miR-21 genes were studied. Apoptosis was determined by using flow cytometry, and apoptotic modifications in signaling pathways were evaluated via Bcl-2, Bax, Caspase-9, and SMAD-4. The co-treatment of GEM and AgNPs increased apoptosis by upregulating Bax and caspase 9 while diminishing Bcl2 and SMAD4. It also improved cytochrome P450 m-RNA relative expression. The results also proved the cooperation between GEM and AgNPs in deactivating miR21. The impact of AgNPs as an adjuvant treatment with GEM was recognized. The study showed that co-treating AgNPs and GEM can improve the efficiency of GEM alone in treating HCC. This is achieved by enhancing intrinsic and extrinsic apoptotic pathways while diminishing some drawbacks of using GEM alone.
吉西他滨（GEM）是一种脱氧胞苷类似物化疗药物，广泛用于治疗多种癌症。银纳米颗粒（AgNPs）是用于治疗多种疾病的重要纳米材料。在纳米颗粒制备中使用γ辐射是一种新型的环保方法。本研究旨在评估吉西他滨和银纳米颗粒联合治疗肝细胞癌的疗效。使用紫外可见光谱、X射线衍射、透射电子显微镜和能谱仪对银纳米颗粒进行了表征。评估了吉西他滨、多柔比星和环磷酰胺对Wi38正常成纤维细胞和HepG2肝癌细胞系的MTT体外细胞毒性。肝癌模型建立后，大鼠每周接受3次（10μg/g体重）的银纳米颗粒，共4周，和/或每周接受2次（5mg/kg体重）的吉西他滨，共4周。检测肝功能酶。研究细胞色素P450和miR-21基因。通过流式细胞术测定细胞凋亡，并通过Bcl-2、Bax、Caspase-9和SMAD-4评估信号通路中的凋亡修饰。吉西他滨和银纳米颗粒联合治疗通过上调Bax和caspase 9增加细胞凋亡，同时降低Bcl2和SMAD4。它还提高了细胞色素P450 mRNA的相对表达。结果还证明了吉西他滨和银纳米颗粒在使miR21失活方面的协同作用。认识到银纳米颗粒作为吉西他滨辅助治疗的作用。该研究表明，联合使用银纳米颗粒和吉西他滨可以提高吉西他滨单独治疗肝癌的疗效。这是通过增强内源性和外源性凋亡途径，同时减少单独使用吉西他滨的一些缺点来实现的。
