AIM: To investigate the effect of alternol on pancreatic cancer cells.METHODS: Pancreatic cancer cells PANC-1 and Bx PC3 were treated with various concentrations of alternol for 24, 48 and 72 h. Cell proliferation was...AIM: To investigate the effect of alternol on pancreatic cancer cells.METHODS: Pancreatic cancer cells PANC-1 and Bx PC3 were treated with various concentrations of alternol for 24, 48 and 72 h. Cell proliferation was measured by cell counting. Cell cycle distribution and mitochondrial membrane potential were determined by flow cytometry. Apoptosis was determined by a Td T-mediated d UTP nick end labeling assay and Hoechst staining. Expression of caspase 3, Bcl-2, p53 and p21 was measured by western blotting.RESULTS: Alternol showed dose- and time-dependent inhibition of the proliferation of PANC-1 and Bx PC3 cells in vitro. Alternol induced apoptosis and cell cycle arrest at S phase and decreased mitochondrial membrane potential. Alternol activated caspase 3, upregulated p53 and p21 expression, and downregulated Bcl-2 expression in a dose-dependent manner.CONCLUSION: Our results suggested that alternol is a candidate for treatment of pancreatic cancer.展开更多
Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However,intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetrati...Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However,intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetration is commonly overlooked. Therefore,in this study,taking fluorescent labeled PLGA(poly(lactic-co-glycolic acid)) nanoparticles as a tool,the influence of anionic and nonionic surfactants on mucus penetration ability of nanoparticles and their mucus barrier regulating ability were studied. The movement of PLGA nanoparticles in mucus was tracked by multiple particles tracking method(MPT).Alteration of mucus properties by addition of surfactants was evaluated by rheology and morphology study. Rat intestinal villus penetration study was used to further evaluate penetration enhancement of nanoparticles. The effective diffusivities of the nanoparticles in surfactants pretreated mucus were increased by 2–3 times and the mucus barrier regulating capacity was also surfactant type dependent. Sodium dodecyl sulfate(SDS) increased the complex viscosity and viscoelastic properties of mucus,but poloxamer presented a decreased trend. Tween 80 maintained the rheological property of the mucus. With the mucus barrier regulated by surfactants,the penetration of nanoparticles in intestinal villus was obviously increased. In summary,the mucus penetration ability of nanoparticles could be enhanced by altering mucus microenvironment with surfactants. Tween 80 which largely retains the original mucus rheology and morphology properties may be a promising candidate for facilitating nanoparticle penetration through the mucus barrier with good safety profile.展开更多
基金Supported by Natural Science Foundation of China,No.81072899Natural Science Foundation of Liaoning Province,No.2013021081Natural Science Foundation of Chongqing,No.cstc2013jcyj A1587
文摘AIM: To investigate the effect of alternol on pancreatic cancer cells.METHODS: Pancreatic cancer cells PANC-1 and Bx PC3 were treated with various concentrations of alternol for 24, 48 and 72 h. Cell proliferation was measured by cell counting. Cell cycle distribution and mitochondrial membrane potential were determined by flow cytometry. Apoptosis was determined by a Td T-mediated d UTP nick end labeling assay and Hoechst staining. Expression of caspase 3, Bcl-2, p53 and p21 was measured by western blotting.RESULTS: Alternol showed dose- and time-dependent inhibition of the proliferation of PANC-1 and Bx PC3 cells in vitro. Alternol induced apoptosis and cell cycle arrest at S phase and decreased mitochondrial membrane potential. Alternol activated caspase 3, upregulated p53 and p21 expression, and downregulated Bcl-2 expression in a dose-dependent manner.CONCLUSION: Our results suggested that alternol is a candidate for treatment of pancreatic cancer.
基金financially supported by the National Natural Science Foundation of China (Grant No. 31870987)
文摘Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However,intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetration is commonly overlooked. Therefore,in this study,taking fluorescent labeled PLGA(poly(lactic-co-glycolic acid)) nanoparticles as a tool,the influence of anionic and nonionic surfactants on mucus penetration ability of nanoparticles and their mucus barrier regulating ability were studied. The movement of PLGA nanoparticles in mucus was tracked by multiple particles tracking method(MPT).Alteration of mucus properties by addition of surfactants was evaluated by rheology and morphology study. Rat intestinal villus penetration study was used to further evaluate penetration enhancement of nanoparticles. The effective diffusivities of the nanoparticles in surfactants pretreated mucus were increased by 2–3 times and the mucus barrier regulating capacity was also surfactant type dependent. Sodium dodecyl sulfate(SDS) increased the complex viscosity and viscoelastic properties of mucus,but poloxamer presented a decreased trend. Tween 80 maintained the rheological property of the mucus. With the mucus barrier regulated by surfactants,the penetration of nanoparticles in intestinal villus was obviously increased. In summary,the mucus penetration ability of nanoparticles could be enhanced by altering mucus microenvironment with surfactants. Tween 80 which largely retains the original mucus rheology and morphology properties may be a promising candidate for facilitating nanoparticle penetration through the mucus barrier with good safety profile.
