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镓纳米颗粒与低剂量γ辐射联合对雌性小鼠的抗癌氧化还原活性

Anticancer redox activity of gallium nanoparticles accompanied with low dose of gamma radiation in female mice.

作者信息

Kandil Eman I, El-Sonbaty Sawsan M, Moawed Fatma Sm, Khedr Ola Ms

机构信息

1 Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.

2 Radiation Microbiology Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.

出版信息

Tumour Biol. 2018 Mar;40(3):1010428317749676. doi: 10.1177/1010428317749676.

Abstract

Guided treatments with nanoparticles and radiotherapy are a new approach in cancer therapy. This study evaluated the beneficial antitumor effects of γ-radiation together with gallium nanoparticles against solid Ehrlich carcinoma in female mice. Gallium nanoparticles were biologically synthesized using Lactobacillus helveticus cells. Transmission electron microscopy showed gallium nanoparticles with size range of 8-20 nm. In vitro study of gallium nanoparticles on MCF-7 revealed IC of 8.0 μg. Gallium nanoparticles (0.1 mg/kg body weight) were injected intraperitoneally daily on the seventh day of Ehrlich carcinoma cells inoculation. Whole-body γ-radiation was carried out at a single dose of 0.25 Gy on eighth day after tumor inoculation. Biochemical analysis showed that solid Ehrlich carcinoma induced a significant increase in alanine aminotransferase activity and creatinine level in serum, calcium, and iron concentrations in liver tissue compared to normal control. Treatment of Ehrlich carcinoma-bearing mice with gallium nanoparticles and/or low dose of γ-radiation exposure significantly reduced tumor volume, decreased alanine aminotransferase and creatinine levels in serum, increased lipid peroxidation, and decreased glutathione content as well as calcium and iron concentrations in liver and tumor tissues with intense DNA fragmentation accompanied compared to untreated tumor cells. Moreover, mitochondria in the treated groups displayed a significant increase in Na+/K+-ATPase, complexes II and III with significant reduction in CYP450 gene expression, which may indicate a synergistic effect of gallium nanoparticles and/or low dose of γ-radiation combination against Ehrlich carcinoma injury, and this results were well appreciated with the histopathological findings in the tumor tissue. We conclude that combined treatment of gallium nanoparticles and low dose of gamma-radiation resulted in suppressive induction of cytotoxic effects on cancer cells.

摘要

纳米颗粒与放射疗法相结合的导向治疗是癌症治疗中的一种新方法。本研究评估了γ射线与镓纳米颗粒联合使用对雌性小鼠实体艾氏癌的有益抗肿瘤作用。利用瑞士乳杆菌细胞生物合成了镓纳米颗粒。透射电子显微镜显示镓纳米颗粒的尺寸范围为8 - 20纳米。镓纳米颗粒对MCF - 7细胞的体外研究显示其半数抑制浓度为8.0微克。在接种艾氏癌细胞的第7天,每天腹腔注射镓纳米颗粒(0.1毫克/千克体重)。在接种肿瘤后的第8天,进行单次剂量为0.25戈瑞的全身γ射线照射。生化分析表明,与正常对照组相比,实体艾氏癌导致血清中丙氨酸转氨酶活性和肌酐水平显著升高,肝脏组织中的钙和铁浓度也显著升高。用镓纳米颗粒和/或低剂量γ射线照射治疗荷艾氏癌小鼠,与未治疗的肿瘤细胞相比,显著减小了肿瘤体积,降低了血清中丙氨酸转氨酶和肌酐水平,增加了脂质过氧化,降低了谷胱甘肽含量以及肝脏和肿瘤组织中的钙和铁浓度,同时伴有强烈的DNA片段化。此外,治疗组的线粒体中Na+/K+-ATP酶、复合物II和III显著增加,CYP450基因表达显著降低,这可能表明镓纳米颗粒和/或低剂量γ射线联合对艾氏癌损伤具有协同作用,这一结果与肿瘤组织的组织病理学发现高度相符。我们得出结论,镓纳米颗粒与低剂量γ射线联合治疗可诱导对癌细胞的细胞毒性抑制作用。

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