ABSTRACT
Objective To investigate the effect of mircoRNA-128-3p (miR-128-3p) on epithelial-mesencfrymal transition (EMT) of ovarian cancer cells and its regulatory mechanism on zinc finger E-box binding homobox 1(ZEB1). Methods Real-time PCR technology was used to detect the expression of miR-128-3p in epithelial ovarian cancer tissue (EOC) and adjacent normal tissue (30 cases each), and to observe whether there was a difference. Two human ovarian cancer cell lines, SK0V3 and A2780, were selected and transfected respectively. MiR-128-3p mimic (miR-128-3p mimic group) and negative control mimic (NC mimic group) were used to detect the expression of miR-128-3p in 4 groups by Real-time PCR to verify the interference effect. Transwell assay was used. The migration and invasion abilities of the four groups of cells were observed. The regulatory relationship between miR-128-3p and ZEBl was verified by dual luciferase assay, and the expression level of ZEBl protein after overexpression of miR-128-3p was detected by Western blotting; pcDNA-ZEBl was transfected into SK0V3 and A2780 cell lines to make it overexpression of ZEBl was divided into NC mimic group, miR-128-3p mimic group, and miR-128-3p mimic+pcDNA-ZEBl group. Western blotting was used to detect the EMT-related protein E-cadherin in 6 groups of cells and the expression level of vimentin. Results Real-time PCR result showed that the expression of miR-128-3p in EOC tissues decreased compared with that in adjacent tissues (P < 0. 01); The relative expression of miR-128-3p in the miR-128-3p mimic group was higher than that in the NC mimic group, while the numbers of migrating cells and invasive cells were lower than those in the NC mimic group (P < 0 . 0 1) . The result of dual luciferase experiments showed that miR-128-3p had a negative regulatory effect on ZEBl. In SK0V3 and A2780 cells, the relative expression of ZEBl protein in the miR-128-3p mimic group was lower than that in the NC mimic group, while the relative protein expression of E-cadhein was higher than that in the NC mimic group (P < 0 . 0 1) . The relative protein expression of E-cadhein in the miR-128-3p mimic+pcDNA-ZEBl group was lower than that in the miR-128-3p mimic group (P < 0 . 0 1) . In SKOV3 and A2780 cells, the relative protein expression of vimentin in the miR-128-3p mimic group was lower than that in the NC mimic group, and the relative protein expression of vimentin in the miR-128-3p mimic+pcDNA-ZEBl group was higher than that in the miR-128-3p mimic group (P < 0 . 0 1) . Conclusion The expression of miR-128-3p decreases in epithelial ovarian cancer tissues, which ma)' be due to the regulation of ZEBl to affect the expression of EMT-related proteins and participate in the EMT process of ovarian cancer cells.
ABSTRACT
The neonatal Fc receptor (FcRn) was first found to be a membrane protein that maternal antibodies transmitted to fetuses and newborns, and also expressed in multiple organs and tissues for whole life in adults. It plays a significant role to central regulate the lifespan of immunoglobulin G and serum albumin, as well as its involvement in innate and adaptive immune responses. In modern biopharmaceuticals, FcRn is a great potential drug delivery target and a highlighted subject for current research. This paper briefly describes the basic biological properties and action mechanism of FcRn, as well as the commonly used drug carrier design strategies of FcRn, especially the functional applications of prolonging half-life, targeted drug delivery, transmembrane and antigen presentation and so on. We propose that these distribution in different tissues and the diverse biological activities may have significant implications of targeting FcRn for novel drug delivery systems and immunotherapy.
ABSTRACT
In the present study, a risperidone loaded microsphere/sucrose acetate isobutyrate (SAIB) in situ forming complex depot was designed to reduce the burst release of SAIB in situ forming depot and to continuously release risperidone for a long-term period without lagime. The model drug risperidone (Ris) was first encapsulated into microspheres and then the Ris-microspheres were embedded into SAIB depot to reduce the amount of dissolved drug in the depot. The effects of different types of microsphere matrix, including chitosan and poly(lactide-coglycolide) (PLGA), matrix/Ris ratios in microspheres and morphology of microspheres on the drug release behavior of complex depot were investigated. In comparison with the Ris-loaded SAIB depot (Ris-SAIB), the complex depot containing chitosan microspheres (in which chitosan/Ris = 1 : 1, w/w) (Ris-Cm-SAIB) decreased the burst release from 12.16% to 5.80%. However, increased drug release rate after 4 days was observed in Ris-Cm-SAIB, which was caused by the high penetration of the medium to Ris-Cm-SAIB due to the hydrophilie of chitosan. By encapsulation of risperidone in PLGA microspheres, most drugs can be prevented from dissolving in the depot and meanwhile the hydrophobic PLGA can reduce the media penetration effect on the depot. The complex depot containing PLGA microspheres (in which PLGA/ drug=4 : 2, w/w) (Ris-Pm-SAIB) showed a significant effectiveness on reducing the burst release both in vitro and in vivo whereby only 0.64% drug was released on the first day in vitro and a low AUC0-4d value [(105.2± 24.4) ng.mL-1.d] was detected over the first 4 days in vivo. In addition, drug release from Ris-Pm-SAIB can be modified by varying the morphology of microspheres. The porous PLGA microspheres could be prepared by adding medium chain triglyceride (MCT) in the organic phase which served as pore agents during the preparation of PLGA microspheres. The complex depot containing porous PLGA microspheres (which were prepared by co-encapsulation of 20% MCT) (Ris-PPm-SAIB) exhibited a slightly increased AUC0-4d of (194.6±15.8) ng.mL-1d and high plasma concentration levels from 4 to 78 days [Cs(4-78d)=(7.8±1.2) ng.mL-1]. The plasma concentration on 78 day C78d was (9.0 2.5) ng.mL-1 which was higher than that of Ris-Pm-SAIB [C78d= (1.6 ± 0.6) ng.mL-1]. In comparison with Ris-Pm-SAIB, the AUC4-78d of Ris-PPm-SAIB increased from (379.0±114.3) ng.mL-1.d to (465.0 ±149.2) ng.mL-1.d, indicating sufficient drug release from the Ris-PPm-SAIB. These results demonstrate that the risperidone loaded porous PLGA microsphere/SAIB in situ forming complex depot could not only efficiently reduce the burst release of SAIB depot both in vitro and in vivo, but also release the drug sufficiently in vivo, and be capable to continuously release the drug for 78 days.