2. Academic Validation
  3. 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

  • Cancer Lett. 2015 Jul 10;363(1):7-16. doi: 10.1016/j.canlet.2015.01.006.
Feng-lei Wu 1,  Ru-Tian Li 2,  Mi Yang 2,  Guo-Feng Yue 3,  Hui-yu Wang 4,  Qin Liu 2,  Fang-bo Cui 5,  Pu-yuan Wu 2,  Hui Ding 2,  Li-Xia Yu 2,  Xiao-Ping Qian 2,  Bao-Rui Liu 6
Affiliations

Affiliations

  • 1 Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, 321 Zhongshan Rd, Nanjing 210008, China; Department of Oncology, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
  • 2 The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, 321 Zhongshan Rd, Nanjing 210008, China.
  • 3 Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
  • 4 Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, 321 Zhongshan Rd, Nanjing 210008, China.
  • 5 The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, 321 Zhongshan Rd, Nanjing 210008, China; Department of Oncology, The People' Hospital of Ma Anshan, Ma Anshan City 243000, Anhui, China.
  • 6 Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, 321 Zhongshan Rd, Nanjing 210008, China. Electronic address: baoruiliu@nju.edu.cn.
PMID: 25592042 DOI: 10.1016/j.canlet.2015.01.006
Abstract

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.

Keywords

Drug delivery; Epigenetic drugs; Hypermethylation; Nanoparticles; TFAP2E.

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