Taha Heba, Elfar Nourhan, Haffez Hesham, Hassan Zeineb A
Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, 11795, Egypt.
Egyptian Drug Authority (EDA), Ministry of Health and Population, Cairo, 11567, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Feb;394(2):279-289. doi: 10.1007/s00210-020-01973-4. Epub 2020 Sep 18.
Raptinal is a novel antineoplastic agent that induces an expeditious intrinsic apoptotic pathway, in addition to the shutdown of mitochondrial function for cancerous cells, because of silver nanoparticles (AgNPs) that have been shown to provide a worthy approach to overcome tumors. In this study, Both Raptinal and Raptinal-loaded silver nanoparticles (AgNPs) were tested as the first time in hepatocellular carcinoma-induced mice to evaluate its efficacy and targeting to HCC. Seventy-two albino male mice of comparable age were classified into six groups; early stage of HCC was induced using diethyl nitrosamine (DEN)/carbon tetrachloride (CCL4). Liver function was assessed in all groups using ALT, AST, total bilirubin, and alpha-fetoprotein (AFP) as well as histopathological examination. Quantitative gene expression of key apoptotic gene markers p53, cytochrome c, and caspase 3 was assessed in all liver homogenates. The results showed that Raptinal-loaded AgNPs group had significant increase in both apoptotic genes of cytochrome c and Caspase 3 at P = 0.0001 compared with Raptinal-free drug group. AFP levels were significantly decreased in Raptinal-loaded AgNPs group compared with both Raptinal-free drug and HCC groups at P = 0.0001. Degenerative changes in the hepatocytes with focal necrosis and inflammatory cell infiltration in histopathology confirm the biochemical analysis. Our study is considered one of the first studies using Raptinal in vivo. Moreover, it showed that Raptinal and/or the combination between Raptinal and AgNPs showed a promising therapeutic agent in treating early HCC.
瑞替那林是一种新型抗肿瘤药物，除了能使癌细胞的线粒体功能停止外，还能诱导快速的内源性凋亡途径，这是因为已证明银纳米颗粒（AgNPs）为克服肿瘤提供了一种有价值的方法。在本研究中，瑞替那林和负载瑞替那林的银纳米颗粒（AgNPs）首次在肝癌诱导的小鼠中进行测试，以评估其对肝癌的疗效和靶向性。将72只年龄相当的白化雄性小鼠分为六组；使用二乙基亚硝胺（DEN）/四氯化碳（CCL4）诱导肝癌早期。使用谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素和甲胎蛋白（AFP）以及组织病理学检查对所有组的肝功能进行评估。在所有肝脏匀浆中评估关键凋亡基因标志物p53、细胞色素c和半胱天冬酶3的定量基因表达。结果显示，与无瑞替那林药物组相比，负载瑞替那林的AgNPs组细胞色素c和半胱天冬酶3这两种凋亡基因均显著增加，P = 0.0001。与无瑞替那林药物组和肝癌组相比，负载瑞替那林的AgNPs组的AFP水平显著降低，P = 0.0001。组织病理学中肝细胞的退行性变化伴局灶性坏死和炎性细胞浸润证实了生化分析。我们的研究被认为是首次在体内使用瑞替那林的研究之一。此外，研究表明瑞替那林和/或瑞替那林与AgNPs的组合在治疗早期肝癌方面显示出有前景的治疗剂。
