Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles
Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles
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伊立替康联合纳米硒的细胞毒性及治疗效果
DOI：
10.1016/j.biomaterials.2014.07.004
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发表时间：
2014-10-01
期刊：
影响因子：
14
通讯作者：
Gao, Xueyun
中科院分区：
文献类型：
--
作者：
Gao, Fuping;Yuan, Qing;Gao, Xueyun
虽然化疗药物广泛应用于临床肿瘤治疗，但严重的毒性制约了其治疗效果。在这项研究中，我们报道了一种新的形式的硒，硒纳米粒子（纳米硒）具有显著的低毒性和良好的生物利用度。研究纳米硒作为抗癌药物伊立替康的化疗预防剂，在体外和体内协同增强抗肿瘤治疗效果。并对其潜在机制进行了研究。纳米硒联合伊立替康对HCT-8肿瘤细胞的细胞毒作用增强，可能是p53介导的细胞凋亡。纳米硒通过半胱天冬酶介导的凋亡部分抑制HCT-8肿瘤细胞的生长。体内实验显示，4 mg/kg/天剂量的纳米硒可显著减轻伊立替康（60 mg/kg）的不良反应。纳米硒单独治疗未引起任何毒性表现。纳米硒联合伊立替康显著抑制HCT-8细胞异种移植瘤的生长，并显著诱导肿瘤细胞凋亡。纳米硒、伊立替康和纳米硒与伊立替康联合使用的肿瘤抑制率分别为17.2%、48.6%和62.1%。纳米硒对肿瘤治疗的有益作用主要归因于选择性调节肿瘤组织和正常组织中的Nrf2-ARE（抗氧化反应元件）通路。研究结果表明，纳米硒是一种很有前途的硒种，在癌症治疗中具有潜在的应用前景。(C) 2014 Elsevier Ltd.版权所有。
Although chemotherapeutic drugs are widely applied for clinic tumor treatment, severe toxicity restricts their therapeutic efficacy. In this study, we reported a new form of selenium, selenium nanoparticles (Nano Se) which have significant lower toxicity and acceptable bioavailability. We investigated Nano Se as chemotherapy preventive agent to protect against toxicities of anticancer drug irinotecan and synergistically enhance the anti-tumor treatment effect in vitro and in vivo. The underlying mechanisms were also investigated. The combination of Nano Se and irinotecan showed increased cytotoxic effect with HCT-8 tumor cells likely by p53 mediated apoptosis. Nano Se inhibited growth of HCT-8 tumor cells partially through caspases mediated apoptosis. In vivo experiment showed Nano Se at a dose of 4 mg/kg/day significantly alleviated adverse effects induced by irinotecan (60 mg/kg) treatment. Nano Se alone treatment did not induce any toxic manifestations. The combination of Nano Se and irinotecan dramatically inhibited tumor growth and significantly induced apoptosis of tumor cells in HCT-8 cells xenografted tumor. Tumor inhibition rate was about 17.2%, 48.6% and 62.1% for Nano Se, irinotecan and the combination of Nano Se and irinotecan, respectively. The beneficial effects of Nano Se for tumor therapy were mainly ascribed to selectively regulating Nrf2-ARE (antioxidant responsive elements) pathway in tumor tissues and normal tissues. Our results suggest Nano Se is a promising selenium species with potential application in cancer treatment. (C) 2014 Elsevier Ltd. All rights reserved.