RESUMO
Halofuginone (HF) is a derivative of dichroine which is the extract of traditional Chinese medicine. It is widely used as an efficient anticoccidial drug. Recent studies have found that HF has unique biological activities, showing great potential capacities in the treatment of autoimmune diseases. In the article, we summarized the therapeutic effects of HF in a variety of autoimmune diseases and its mechanism, providing references for further clinical studies of HF.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Piperidinas/uso terapêutico , Quinazolinonas/uso terapêutico , Humanos , Medicina Tradicional ChinesaRESUMO
Inflammation is regarded as one of the major hallmarks of tumors, and has a very close relationship with gastric cancer. Interleukin-33 (IL-33), a new member of the IL-1 family, plays an important role in both inflammatory disease and tumors. The present study was designed to explore the effects of IL-33 on the proliferation, drug sensitivity, and the invasiveness of gastric cancer cells in vitro. IL-33 at concentrations lower than 100 pg/ml did not alter the inhibitory rate of gastric cancer cells. Moreover, IL-33 at these low concentrations protected against platinum-induced apoptosis in various gastric cancer cell lines, yet not in normal gastric epithelial cells. We also found that IL-33 increased the activation of the JNK pathway, and enhanced the expression of ST2. Furthermore, SP600125, a selective inhibitor of the JNK pathway, significantly blocked the protective effects of IL-33 in gastric cancer cells. In addition, Matrigel invasion assay showed that IL-33 markedly promoted gastric cancer cell invasion. In conclusion, the present study demonstrated that IL-33 protected against platinum-induced apoptosis and promoted cell invasion via activation of the JNK pathway in gastric cancer cells. In light of the prevalence of platinum-based chemotherapeutics in the treatment of gastric cancer, our results suggest that the level of IL-33 should be monitored during the treatment of gastric cancer, particularly when using platinum-based chemotherapeutics.
Assuntos
Inflamação/genética , Interleucina-33/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Gástricas/genética , Antracenos/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Interleucina-33/administração & dosagem , Sistema de Sinalização das MAP Quinases/genética , Invasividade Neoplásica/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologiaRESUMO
Stoppin (L1) is a newly identified anticancer peptide, which is a potent p53MDM2/MDMX inhibitor. Due to its limitation in cell delivery efficiency, a new peptide delivery system was developed based on a nucleic acidpolypeptideliposome complex and its stability and effectiveness in vitro was investigated. The nucleic acidstoppinliposome complex was prepared and characterization of the complex was conducted. The stability of the complex was evaluated by enzyme digestion. Following transfection of the A549 cells with the complex, detection of green fluorescent protein (GFP) and luciferase activity was conducted to evaluate transfection efficiency. In addition, the anticancer activity of the complex was determined by 3(4,5dimethylthiazolyl2)2,5 diphenyltetrazolium bromide assay and apoptosis was detected by flow cytometry. The results indicated that the particle size of the complex was 102±10 nm and the encapsulation rate was ~100% when the ratio of liposome, L1 and plasmid was: 4 µl:1 µg:2 µg. The enzyme digestion experiment demonstrated that the complex was resistant to pancreatic and DNA enzyme degradation, indicating that the complex had biological stability. Cell transfection demonstrated that it had a mutual promotion effect on delivery, which could be confirmed by GFP fluorescence and luciferase assay. The cellkilling efficiency of this novel delivery system was three times higher than with stoppin alone at a low concentration. In conclusion, this novel stoppin peptide delivery system was stable. The nucleic acidpeptideliposome complex can protect the internal component from the degradation of enzymes, promote entry of the peptide into the cells and enhance the antitumor activity of stoppin. Therefore, it is a promising approach for peptide delivery, which can be characterized and visualized using plasmids with GFP or luciferase.