Nabeel Asmaa I
Biochemistry Laboratory, Chemistry Department, Faculty of Education, Ain Shams University, Cairo, Egypt.
Tumour Biol. 2020 Mar;42(3):1010428320909999. doi: 10.1177/1010428320909999.
Cancer is the leading cause of death and exhausts human and economic resources for treatment and protection. Zinc oxide nanoparticles play an effective role in tumor treatment but with some cautions, such as overexpression of cytochrome P450, hepatic overload, and the mammalian target of rapamycin pathway resistance. Although lanthanides have antitumor activity, their use is limited. Therefore, the current study aims to improve the effectiveness of zinc oxide nanoparticle via doping with lanthanides, such as samarium. In vitro study revealed that samarium doped with zinc oxide showed more antitumor activity than the other lanthanides, and the antitumor activity depends on the concentration of samarium in the nanocomposite. The in vivo experiment on mice bearing Ehrlich solid tumor revealed that intramuscular injection of samarium/zinc oxide downregulates the expressions of CXCR4 and PI3K/Akt/mammalian target of rapamycin pathway in respect to Ehrlich solid tumor group. Regarding the apoptotic biomarkers, samarium/zinc oxide upregulates the apoptotic biomarker; Bax accompanied with the mitotic catastrophe which was indicated by cell cycle arrest in G2 phase. Moreover, samarium:zinc oxide nanoparticles exhibited minimum toxicity which was indicated by suppressed activities of cytochrome P450 and hepatic enzymes, including alanine transaminase and aspartate transaminase. In addition, the histopathological finding, as well as immunophenotyping results, appreciated the biochemical finding. Therefore, samarium:zinc oxide might be offered a new approach to improve the effectiveness of zinc oxide nanoparticles along with lower toxic effect. Also, samarium:zinc oxide nanoparticles can be a candidate as a new antitumor compound to detect its mode of action.
癌症是主要的死亡原因，耗尽了用于治疗和防护的人力和经济资源。氧化锌纳米颗粒在肿瘤治疗中发挥着有效作用，但也存在一些需要注意的问题，例如细胞色素P450的过表达、肝脏负荷过重以及雷帕霉素靶蛋白通路抗性。尽管镧系元素具有抗肿瘤活性，但其应用受到限制。因此，当前的研究旨在通过掺杂镧系元素（如钐）来提高氧化锌纳米颗粒的有效性。体外研究表明，掺杂钐的氧化锌比其他镧系元素表现出更强的抗肿瘤活性，且抗肿瘤活性取决于纳米复合材料中钐的浓度。对荷艾氏实体瘤小鼠的体内实验表明，相对于艾氏实体瘤组，肌肉注射钐/氧化锌可下调CXCR4和PI3K/Akt/雷帕霉素靶蛋白通路的表达。关于凋亡生物标志物，钐/氧化锌上调凋亡生物标志物；Bax伴随着有丝分裂灾难，这表现为细胞周期阻滞在G2期。此外，钐:氧化锌纳米颗粒表现出最小的毒性，这通过细胞色素P450以及包括丙氨酸转氨酶和天冬氨酸转氨酶在内的肝脏酶活性受到抑制得以表明。另外，组织病理学发现以及免疫表型分析结果证实了生化发现。因此，钐:氧化锌可能为提高氧化锌纳米颗粒的有效性以及降低毒性作用提供一种新方法。而且，钐:氧化锌纳米颗粒可以作为一种新型抗肿瘤化合物的候选物来检测其作用方式。
