Hassan Hesham Fathy Hassan, Mansour Ahmed Mohamed, Abo-Youssef Amira Morad Hussein, Elsadek Bakheet E M, Messiha Basim Anwar Shehata
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Clin Exp Pharmacol Physiol. 2017 Feb;44(2):235-243. doi: 10.1111/1440-1681.12681.
Currently, the outcomes of conventional chemotherapeutic approaches are unsatisfactory. Clinical application of nanoparticles seems promising. We aim to evaluate the possible antitumor activity of zinc oxide nanoparticles (ZnONPs) as a chemotherapeutic approach in in vitro and in vivo experimental models. An in vitro study was performed on three different cell lines, namely human hepatocellular carcinoma (HEPG2), human prostate cancer (PC3), and none-small cell lung cancer (A549) cell lines. An in vivo study using diethylnitrosamine (DENA)-induced HCC in adult male Wistar rats was conducted to investigate the potential antitumor activity of ZnONPs in HCC and the possible underlying mechanisms. Hepatocellular carcinoma (HCC) was induced by oral administration of DENA given in drinking water (100 mg/L) for 8 weeks. Rats were allocated into four groups, namely a control group, an HCC control group receiving DENA alone, a ZnONPs (10 μg/kg per week, intravenous (i.v.) for 1 month) control group, and a ZnONPs treatment group (receiving ZnONPs + DENA). ZnONPs significantly reduced the elevated serum levels of HCC-related tumor markers alphafetoprotein and alpha-l-fucosidase and the apoptotic marker caspase-3 compared with the untreated HCC rats. In addition, treatment with ZnONPs significantly decreased the elevated levels of hepatocyte integrity and oxidative stress markers as compared with the untreated HCC control group. Furthermore, the histopathological study revealed anaplasia and fibrous degenerations which were significantly corrected by ZnONPs treatment. In conclusion, administration of ZnONPs exhibited a promising preclinical anticancer efficacy in HCC and could be considered as a novel strategy for the treatment HCC in clinical practices.
目前，传统化疗方法的效果并不理想。纳米颗粒的临床应用似乎很有前景。我们旨在评估氧化锌纳米颗粒（ZnONPs）作为一种化疗方法在体外和体内实验模型中的潜在抗肿瘤活性。对三种不同的细胞系进行了体外研究，即人肝癌（HEPG2）、人前列腺癌（PC3）和非小细胞肺癌（A549）细胞系。使用二乙基亚硝胺（DENA）诱导成年雄性Wistar大鼠发生肝癌进行体内研究，以探讨ZnONPs在肝癌中的潜在抗肿瘤活性及可能的潜在机制。通过在饮用水中口服给予DENA（100mg/L）8周来诱导肝癌。将大鼠分为四组，即对照组、仅接受DENA的肝癌对照组、ZnONPs（每周10μg/kg，静脉注射（i.v.）1个月）对照组和ZnONPs治疗组（接受ZnONPs + DENA）。与未治疗的肝癌大鼠相比，ZnONPs显著降低了肝癌相关肿瘤标志物甲胎蛋白和α-L-岩藻糖苷酶以及凋亡标志物caspase-3的血清水平升高。此外，与未治疗的肝癌对照组相比，ZnONPs治疗显著降低了肝细胞完整性和氧化应激标志物的升高水平。此外，组织病理学研究显示了间变和纤维变性，而ZnONPs治疗显著纠正了这些病变。总之，给予ZnONPs在肝癌中显示出有前景的临床前抗癌疗效，可被视为临床实践中治疗肝癌的一种新策略。
