Gelatinases-stimuli nanoparticles encapsulating 5-fluorouridine and 5-aza-2′-deoxycytidine enhance the sensitivity of gastric cancer cells to chemical therapeutics
Gelatinases-stimuli nanoparticles encapsulating 5-fluorouridine and 5-aza-2′-deoxycytidine enhance the sensitivity of gastric cancer cells to chemical therapeutics
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封装5-氟尿苷和5-氮杂-2-脱氧胞苷的明胶酶刺激纳米颗粒增强胃癌细胞对化学治疗的敏感性
DOI：
10.1016/j.canlet.2015.01.006
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发表时间：
2015-07-10
期刊：
影响因子：
9.7
通讯作者：
Liu, Bao-Rui
中科院分区：
文献类型：
--
作者：
Wu, Feng-lei;Li, Ru-Tian;Liu, Bao-Rui
转录因子AP-2 epsilon （TFAP2E）的异常甲基化归因于5-氟吡啶（5-FU）敏感性。5-Aza-2′-脱氧胞苷（DAC）是一种抑制DNA甲基化的表观遗传药物，能够通过去甲基化活性引起TFAP2E的反应性表达。这一特性可能有助于提高癌细胞对5-FU的敏感性。然而，由于DAC本身的不稳定性，其影响是短暂的。在这里，我们报道了使用智能明胶酶刺激纳米颗粒（NPs）来共包并递送DAC和5-FU到胃癌（GC）细胞。结果表明，包封DAC、5-FU或两者的NPs可被GC细胞有效内化。此外，我们发现NPs增强了DAC的稳定性，从而改善了TFAP2E的再表达。由此可见，DAC掺入NPs后，通过抑制细胞生长速率和诱导细胞凋亡，显著增强GC细胞对5-FU的敏感性。总之，本研究的结果清楚地表明，明胶酶刺激NPs是同时递送表观遗传和化疗药物的有效手段，可能有效抑制癌细胞增殖。2015爱思唯尔爱尔兰有限公司版权所有。
Aberrant methylation of the transcription factor AP-2 epsilon (TFAP2E) has been attributed to 5-fluorouridine (5-FU) sensitivity. 5-Aza-2'-deoxycytidine (DAC), an epigenetic drug that inhibits DNA methylation, is able to cause reactive expression of TFAP2E by demethylating activity. This property might be useful in enhancing the sensitivity of cancer cells to 5-FU. However, the effect of DAC is transient because of its instability. Here, we report the use of intelligent gelatinases-stimuli nanoparticles (NPs) to coencapsulate and deliver DAC and 5-FU to gastric cancer (GC) cells. The results showed that NPs encapsulating DAC, 5-FU, or both could be effectively internalized by GC cells. Furthermore, we found that the NPs enhanced the stability of DAC, resulting in improved re-expression of TFAP2E. Thus, the incorporation of DAC into NPs significantly enhanced the sensitivity of GC cells to 5-FU by inhibiting cell growth rate and inducing cell apoptosis. In conclusion, the results of this study clearly demonstrated that the gelatinases-stimuli NPs are an efficient means to simultaneously deliver epigenetic and chemotherapeutic drugs that may effectively inhibit cancer cell proliferation. (C) 2015 Elsevier Ireland Ltd. All rights reserved.