Prylutska Svitlana, Grynyuk Iryna, Matyshevska Olga, Prylutskyy Yuriy, Evstigneev Maxim, Scharff Peter, Ritter Uwe
Joint Ukrainian-German Center on Nanobiotechnology, Kyiv, Ukraine.
Drugs R D. 2014 Dec;14(4):333-40. doi: 10.1007/s40268-014-0074-4.
Doxorubicin (Dox) is one of the most potent anticancer drugs, but its successful use is hampered by high toxicity caused mainly by generation of reactive oxygen species. One approach to protect against Dox-dependent chemical insult is combined use of the cytostatic drug with antioxidants. C60 fullerene has a nanostructure with both antioxidant and antitumor potential and may be useful in modulating cell responses to Dox.
The aim of this study was to estimate the antitumor effect and antioxidant enzyme activity of combined C60 fullerene and Dox (C60 + Dox) in the liver and heart of mice with Lewis lung carcinoma compared with Dox treatment alone.
Highly stable pristine C60 fullerene aqueous colloid solution (concentration 1.0 mg/ml, average hydrodynamic diameter of nanoparticles 50 nm) was used in the study and characterized by means of atomic force microscopy (AFM). The in vivo investigation of C60-Dox action was performed via the standard methods of histological and enzyme activity analyses.
Dox (total dose 2.5 mg/kg) combined with C60 fullerene (total dose 25 mg/kg) in tumor-bearing animals resulted in tumor growth inhibition, prolongation of life, metastasis inhibition, and increased number of apoptotic tumor cells and was more effective than the corresponding course of Dox treatment alone. C60 fullerene demonstrated a protective effect against superoxide dismutase and glutathione peroxidase inhibition induced by Dox-dependent oxidative insult in the liver and heart.
Combined treatment with C60 + Dox is considered to be a promising approach for cancer chemotherapy.
阿霉素（Dox）是最有效的抗癌药物之一，但其成功应用受到主要由活性氧生成所导致的高毒性的阻碍。一种预防阿霉素依赖性化学损伤的方法是将细胞抑制药物与抗氧化剂联合使用。C60富勒烯具有兼具抗氧化和抗肿瘤潜力的纳米结构，可能有助于调节细胞对阿霉素的反应。
本研究旨在评估与单独使用阿霉素治疗相比，C60富勒烯与阿霉素联合使用（C60 + Dox）对Lewis肺癌小鼠肝脏和心脏的抗肿瘤作用及抗氧化酶活性。
本研究使用了高度稳定的原始C60富勒烯水胶体溶液（浓度1.0 mg/ml，纳米颗粒平均流体动力学直径50 nm），并通过原子力显微镜（AFM）进行表征。通过组织学和酶活性分析的标准方法对C60 - Dox的作用进行体内研究。
在荷瘤动物中，阿霉素（总剂量2.5 mg/kg）与C60富勒烯（总剂量25 mg/kg）联合使用可抑制肿瘤生长、延长生存期、抑制转移并增加凋亡肿瘤细胞数量，且比单独使用相应疗程的阿霉素治疗更有效。C60富勒烯对阿霉素依赖性氧化损伤诱导的肝脏和心脏中超氧化物歧化酶和谷胱甘肽过氧化物酶的抑制具有保护作用。
C60 + Dox联合治疗被认为是一种有前景的癌症化疗方法。
