RESUMEN
OBJECTIVE: Endometrial cancer (EC) is a prevalent gynecologic malignancy. The critical role of PTPN18 in EC has been reported, while its role in the aerobic glycolysis of EC cells remains unclear. Our current study focused on the mechanism of PTPN18 in the regulation of aerobic glycolysis in EC. METHODS: PTPN18 expression levels in endometrial stromal cells (KC02-44D) and EC cells (KLE, HEC-1-A, HEC-1B, and HEC-50) were determined. Following transfection of sh-PTPN18 in HEC-1-A cells, the changes in cell migratory and invasive abilities were assessed by the Transwell assay, and the changes in glucose consumption, lactic acid secretion, and ATP levels were detected using kits. The expression levels of glycolysis-related proteins HIF-1α, PKM2, and LDHA and the activation of the MYC/PI3K/AKT pathway were detected by Western blot. Additionally, sh-PTPN18 and pcDNA3.1-MYC were transfected into HEC-1-A cells to further explore their roles in the changes in aerobic glycolysis, migration, and invasion ability of EC cells. RESULTS: Expression of PTPN18 in EC cells was up-regulated (HEC-1-A>HEC-1B>HEC-50>KLE). PTPN18 knockdown suppressed EC cell migration and invasion. Additionally, PTPN18 knockdown reduced glucose consumption, lactate production, ATP levels, and glycolysis-related protein levels (HIF-1α, PKM2, LDHA). PTPN18 knockdown inhibited the activation of the MYC/PI3K/AKT pathway in EC cells. MYC overexpression partially annulled the inhibitory effects of PTPN18 knockdown on aerobic glycolysis, migration, and invasion of EC cells. CONCLUSION: Our present study provided evidence that the knockdown of PTPN18 inhibited the aerobic glycolysis, migration, and invasion of EC cells by suppressing the MYC/PI3K/AKT pathway.
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Here, an efficient leaving group-activated methylene alcohol strategy for the preparation of primary propargyl alcohols from terminal alkynes by employing the bulk industrial product rongalite as the C1 unit has been described. The reaction avoids the low-temperature reaction conditions and inconvenient lithium reagents required for the classical method of preparing primary propargylic alcohols. Preliminary mechanistic studies showed that the reaction may not proceed via formaldehyde intermediates, but through the direct nucleophilic attack of the terminal alkyne on the carbon atom of rongalite by activation through SO2- as a leaving group.
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As the outmost coating of cells, the pericellular matrix (PCM) involved in various cellular functions has been exploited previously to be able to accumulate 120 nm Au nanoparticles (NPs), adjust their diffusion coefficient similar to that of membrane receptors, and enhance their uptake efficiency. In this study, the interactions between PCM and NPs with different sizes and materials were systematically investigated. We found that PCM can selectively enhance the retention and cellular uptake of NPs with diameters from 50 to 180 nm, but has no enhancement effect for 20 nm NPs. Identical behaviors of PCM was observed for both Au NPs and polystyrene NPs, indicating that this unique phenomenon is more related to the dimensions of the NPs. The study of single-particle tracking of 50-180 nm NPs on the surface of thick PCM cells revealed that PCM actively adjusts the diffusion coefficient of NPs to â¼0.1 µm(2)/s regardless of their sizes. By blocking the receptor-mediated endocytosis (RME) pathway with four different inhibitors, this active role of PCM can be effectively suppressed, further confirming that the trapping and retention of NPs by PCM is an inherent biological function. These findings provided new insights for better understanding of the RME pathway and may have promising NP-based applications for controlled drug delivery and therapy in biomedicine.
Asunto(s)
Portadores de Fármacos/química , Endocitosis/fisiología , Oro/química , Nanopartículas del Metal/química , Osteosarcoma/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Citocalasina D/farmacología , Endocitosis/efectos de los fármacos , Células HeLa , Humanos , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Tamaño de la Partícula , Propiedades de Superficie , Células Tumorales CultivadasRESUMEN
We have prepared enzyme-mimic Au-Pt nanocomposites (NCs) for catalyzing the decomposition of reactive oxygen species. After surface modification, the Au-Pt NCs can be readily internalized and retained by human skin cells and also can effectively reduce cellular oxidative stress. We have demonstrated that the active and biocompatible Au-Pt nanocomposites can be applied for preventing cell damages by scavenging cellular reactive oxygen species induced by ultraviolet irradiation, indicating potential uses for the prevention and therapy of ROS-mediated diseases.