ABSTRACT
Non-small cell lung cancer (NSCLC) is a common pathological type of lung cancer, which has a serious impact on human life, health, psychology and life. At present, chemotherapy, targeted therapy and other methods commonly used in clinic are prone to drug resistance and toxic side effects. Natural extracts of traditional Chinese medicine (TCM) have attracted wide attention in cancer treatment because of their small toxic and side effects. Kaempferol is a flavonoid from natural plants, which has been proved to have anticancer properties in many cancers such as lung cancer, but the exact molecular mechanism is still unclear. Therefore, on the basis of in vitro experiments, we used network pharmacology and molecular docking methods to study the potential mechanism of kaempferol in the treatment of non-small cell lung cancer. The target of kaempferol was obtained from the public database (PharmMapper, Swiss target prediction), and the target of non-small cell lung cancer was obtained from the disease database (Genecards and TTD). At the same time, we collected gene chips GSE32863 and GSE75037 in conjunction with GEO database to obtain differential genes. By drawing Venn diagram, we get the intersection target of kaempferol and NSCLC. Through enrichment analysis, PI3K/AKT is identified as the possible key signal pathway. PIK3R1, AKT1, EGFR and IGF1R were selected as key targets by topological analysis and molecular docking, and the four key genes were further verified by analyzing the gene and protein expression of key targets. These findings provide a direction for further research of kaempferol in the treatment of NSCLC.
ABSTRACT
Astragalus membranaceus Bunge is widely used in Traditional Chinese Medicine to treat various cancers. AstragalosideIV (ASIV) is one of the major compounds isolated from A. membranaceus Bunge and has been demonstrated to have antitumor effects by inhibiting cell proliferation, invasion and metastasis in various cancer types. Numerous studies have used in vitro cell culture and in vivo animal models of cancer to explore the antitumor activities of ASIV. In the present study, the antitumor effects and mechanisms of ASIV reported in studies recorded in the PubMed database were reviewed. First, the antitumor effects of ASIV on proliferation, cell cycle, apoptosis, autophagy, invasion, migration, metastasis and epithelialmesenchymal transition processes in cancer cells and the tumor microenvironment, including angiogenesis, tumor immunity and macrophagerelated immune responses to cancer cells, were comprehensively discussed. Subsequently, the molecular mechanisms and related signaling pathways associated with antitumor effects of ASIV as indicated by in vitro and in vivo studies were summarized, including the Wnt/AKT/GSK-3ß (glycogen synthase kinase3ß)/ßcatenin, TGFß/PI3K/AKT/mTOR, PI3K/MAPK/mTOR, PI3K/AKT/NFκB, Rac family small GTPase 1/RAS/MAPK/ERK, TNFα/protein kinase C/ERK1/2NFκB and Tregs (Tregulatory cells)/IL11/STAT3 signaling pathways. Of note, several novel mechanisms of Tolllike receptor 4 (TLR4)/NFκB/STAT3, pSmad3C/3L, nuclear factor erythroid 2related factor (NrF2)/heme oxygenase 1, circDLST/microRNA4893p/eukaryotic translation initiation factor 4A1 and macrophagerelated highmobility group box 1TLR4 signaling pathways associated with the anticancer activity of ASIV were also included. Finally, the limitations of current studies that must be addressed in future studies were pointed out to facilitate the establishment of ASIV as a potent therapeutic drug in cancer treatment.
Subject(s)
Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Animals , Apoptosis , Cell Line, Tumor , Cell Proliferation , Glycogen Synthase Kinase 3 beta , NF-kappa B , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Toll-Like Receptor 4 , TOR Serine-Threonine Kinases/metabolismABSTRACT
How to improve the bioavailability of the Sanguis Draconis (SD) is an important problem in the potential clinical applications. The aim of this study was to develop a drug delivery system to achieve high bioavailability of SD, a drug with poor water solubility. It will promote the research about new formulations of the SD and the other insoluble drugs. In this study, a highly biocompatible hydrophilic polymer, polyvinylpyrrolidone (PVP), was selected as a carrier, mixed with different proportions of SD to produce SD-PVP microfibers by solution electrospinning. By orthogonal experiments, the optimal spinning conditions of the preparation of SD-PVP fibers were investigated. The morphology of different proportions of SD-PVP microfibers was observed by scanning electron microscopy, and the phase characteristics were characterized by Fourier transform infrared spectrometry, X-ray diffraction, and differential scanning calorimetry. The hydrophilic properties of SD-PVP fiber membranes with different SD content were analyzed by the water contact angle assay. In vitro dissolution experiments were carried out to observe the dissolution of drugs in SD-PVP fiber membranes. The results showed that the diameter of SD-PVP fibers increased with the enlargement of SD content. A eutectic mixture was formed after blending PVP and SD, and the hydrogen bonds were formed between the SD and PVP with no chemical reaction occurred. The dispersion of SD in the fiber decreased with the increase of SD content. The higher the content of SD in the fiber, the more hydrophobic the fiber membrane. In vitro dissolution studies revealed that the dissolution content of SD from SD-PVP microfibers was significantly higher than that of the pure or original drug SD. However, as the SD content increased from 15% to 30%, the dissolution of the drug in the SD-PVP fibers decreased. The SD-PVP fiber prepared in this study showed much higher solubility than the original drug in vitro, which has great significance for the development of new dosage forms for the clinical application of SD, and it has a useful reference for the study of similar bioavailability of poorly soluble drugs.