ABSTRACT
MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.
ABSTRACT
Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and lasers. The ultrasmall superparamagnetic iron oxide nanoparticles (USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin (Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.
ABSTRACT
The dynamic or flowing tumor cells just as leukemia cells and circulating tumor cells face a microenvironment difference from the solid tumors, and the related targeting nanomedicines are rarely reported. The existence of fluidic shear stress in blood circulation seems not favorable for the binding of ligand modified nanodrugs with their target receptor. Namely, the binding feature is very essential in this case. Herein, we utilized HSPC, PEG-DSPE, cholesterol and two
ABSTRACT
To establish an injectable hydrogel containing Prussian blue (PB) nanospheres for photothermal therapy against cancer, PB nanospheres were prepared by one-pot synthesis and the thermosensitive Pluronic F127 was used as the hydrogel matrix. The PB nanospheres and the hydrogel were characterized by shape, particle size, serum stability, photothermal performance upon repeated 808 nm laser irradiation, as well as the rheological features. The effect of the PB nanospheres and the hydrogel were evaluated qualitatively and quantitatively in 4T1 mouse breast cancer cells. The retention, photothermal efficacy, therapeutic effects and systemic toxicity of the hydrogel were assessed in a tumor-bearing mouse model. The PB nanospheres had a diameter of about 150 nm and exhibited satisfactory serum stability, photo-heat convert ability and repeated laser exposure stability. The hydrogel encapsulation did not negatively influence the above features of the photothermal agent. The nanosphere-containing hydrogel showed a phase transition at body temperature and, as a result, a long retention time . The photothermal agent-embedded hydrogel displayed promising photothermal therapeutic effects in the tumor-bearing mouse model with little-to-no systemic toxicity after peritumoral administration.
ABSTRACT
Objective To discuss the clinical effect and safety on rosiglitazone applied to patients with early type 2 diabetic nephropathy.Methods Ninety-six patients with early type 2 diabetic nephropathy were divided into the control group(n=48) and the research group (n =48).The patients of the control group were given mefformin treatment, while of research group were given rosiglitazone, both the courses were three months.The urinary albumin excretion rate (UAER), 24 h urine trace albumin (UAE), serum creatinine clearance (SCr) , fasting plasma glucose (FPG), postprandial blood glucose (2 hPG), glycosylated hemoglobin (HbA 1 c), triglycerides (TG), cholesterol (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) before and after treatment and clinical effect between the two groups were compared.Results The HbA1c, FPG, 2 hPG, UAER, UAE, TC, TG of after treatment of all patients decreased obviously,while the HDL-C level increased remarkably, and compared with control group the differences were significant (HbA1 c: (7.32±0.84)％ vs (7.56±0.98)％, FPG: (8.02± 1.42) mmol/L vs (8.16± 1.54) mmol/L, 2 hPG: (11.54±2.11) mmol/L vs (12.02±1.97) mmol/L,UAER: (67.34±6.45) mg/24 h vs (52.56±5.35) mg/24 h,UAE: (108.64±22.64) mg/d vs (68.84± 11.43) mg/d, TC : (5.44± 0.72) mmol/L vs (4.76± 0.51) mmol/L, TG: (2.04± 0.53) mmol/L) vs (1.73±0.46) mmol/L);t =-4.172,-3.973,-4.026,-4.263,-6.634,-5.737,-5.635, -4.735,-4.633;P＜O.05).While there were no statistical significance about SCr before and after treatment(P ＞0.05).The total clinical effect of the research group was obviously higher than that of the control group (87.5％ (42/48) vs 66.7％ (32/48), x2 =5.363,P =0.035).There were not obvious adverse reaction occurred during treatment for all patients.Conclusion Rosiglitazone can effectively reduce the blood glucose in patients with early type 2 diabetic nephropathy and reduce urinary protein excretion, the effect is more obvious than that of metformin.