Gelatinases-stimuli nanoparticles encapsulating 5-fluorouridine and 5-aza-2'-deoxycytidine enhance the sensitivity of gastric cancer cells to chemical therapeutics.

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.

• Authors: Feng-lei Wu, Ru-Tian Li, Mi Yang, Guo-Feng Yue, Hui-yu Wang, Qin Liu, Fang-bo Cui, Pu-yuan Wu, Hui Ding, Li-Xia Yu, Xiao-Ping Qian, Bao-Rui Liu
• Journal: Cancer letters (Cancer Lett) Vol. 363 Issue 1 Pg. 7-16 (Jul 10 2015) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 25592042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• TFAP2E protein, human
• Transcription Factor AP-2
• Decitabine
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9
• Azacitidine
• Fluorouracil

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Azacitidine (analogs & derivatives, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chemistry, Pharmaceutical
• DNA Methylation (drug effects)
• Decitabine
• Dose-Response Relationship, Drug
• Drug Stability
• Enzyme Activation
• Epigenesis, Genetic (drug effects)
• Fluorouracil (chemistry, pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Nanoparticles
• Stomach Neoplasms (enzymology, genetics, pathology)
• Time Factors
• Transcription Factor AP-2 (genetics, metabolism)