Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells.
Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells.
复制标题
负载 miR-200c 的明胶酶刺激 PEG-Pep-PCL 纳米粒子增强胃癌细胞的放疗效果
DOI：
10.2147/ijn.s60874
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发表时间：
2014
影响因子：
8
通讯作者：
Liu BR
中科院分区：
文献类型：
--
作者：
Cui FB;Liu Q;Li RT;Shen J;Wu PY;Yu LX;Hu WJ;Wu FL;Jiang CP;Yue GF;Qian XP;Jiang XQ;Liu BR
放射治疗是包括胃癌在内的许多类型的不可切除肿瘤的主要局部控制方式。然而，许多患者由于癌细胞的固有辐射抗性而失败放射治疗，这已被发现与癌症干细胞（CSC）样性质密切相关。在这项研究中，我们开发了一种纳米颗粒制剂来递送miR-200 c，据报道，miR-200 c可以抑制CSC样特性，然后评估其作为放射增敏剂的潜在活性。miR-200 c纳米颗粒显著增强了三种胃癌细胞系的放射敏感性（增敏比1.13-1.25），但仅轻微增强了GES-1细胞（1.06）。除了放射增强作用外，miR-200 c纳米颗粒还降低了CD 44（一种推定的CSC标志物）的表达和CD 44 + BGC 823细胞的百分比。与此同时，其他CSC样特性，包括侵袭性和抗凋亡性，可以被miR-200 c纳米颗粒抑制。CSC相关的辐射抗性机制，包括活性氧水平和DNA修复能力，也被削弱。我们已经证明miR-200 c纳米颗粒是胃癌细胞中有效的放射增敏剂，并且对正常细胞几乎不诱导放射增敏，这表明它们是进一步临床前和临床评价的有希望的候选物。
Radiotherapy is the main locoregional control modality for many types of unresectable tumors, including gastric cancer. However, many patients fail radiotherapy due to intrinsic radioresistance of cancer cells, which has been found to be strongly associated with cancer stem cell (CSC)-like properties. In this study, we developed a nanoparticle formulation to deliver miR-200c, which is reported to inhibit CSC-like properties, and then evaluated its potential activity as a radiosensitizer. miR-200c nanoparticles significantly augmented radiosensitivity in three gastric cancer cell lines (sensitization enhancement ratio 1.13–1.25), but only slightly in GES-1 cells (1.06). In addition to radioenhancement, miR-200c nanoparticles reduced the expression of CD44, a putative CSC marker, and the percentage of CD44+ BGC823 cells. Meanwhile, other CSC-like properties, including invasiveness and resistance to apoptosis, could be suppressed by miR-200c nanoparticles. CSC-associated radioresistance mechanisms, involving reactive oxygen species levels and DNA repair capacity, were also attenuated. We have demonstrated that miR-200c nanoparticles are an effective radiosensitizer in gastric cancer cells and induce little radiosensitization in normal cells, which suggests that they are as a promising candidate for further preclinical and clinical evaluation.