ABSTRACT
Although microRNAs and EIF4G2 are both known to play pivotal roles in cancer progression, it remains unknown whether these pathways regulate chemosensitivity in a coordinated manner. Here, we show that miR-379 expression is significantly downregulated in chemoresistant nonsmall cell lung cancer (NSCLC) tissues and cells. Manipulation of miR-379 levels could alter the in vitro and in vivo cisplatin (CDDP) resistance in lung cancer (LCa) cells. Mechanistically, miR-379 potentiated LCa chemosensitivity via modulation of CDDP-induced apoptosis by directly targeting the EIF4G2 3'UTR. Additionally, we observed an inverse correlation between miR-379 and EIF4G2 expression in LCa tissues from patients with CDDP-based chemotherapy. Together, our findings shed new light on the potential involvement of miR-379/EIF4G2 cascade in the pathogenesis of CDDP resistance in LCa.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/pharmacology , Eukaryotic Initiation Factor-4G/genetics , Lung Neoplasms/drug therapy , MicroRNAs/genetics , 3' Untranslated Regions/genetics , A549 Cells , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Base Sequence , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line , Cell Line, Tumor , Eukaryotic Initiation Factor-4G/metabolism , Gene Expression Regulation, Neoplastic , HEK293 Cells , Humans , Immunoblotting , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Mice, Nude , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Amino Acid , Xenograft Model Antitumor AssaysABSTRACT
Objective: To prepare porosity osmotic pump tablets of total glucosides of paeony( TGP),and to study the behavior on synchronous release of its main components. Methods: Taking the accumulative release of TGP as indexes, through single-factor test and orthogonal design to investigate the optimal formulation porosity osmotic pump tablets of TGP. The main components, paeoniflorin, albiflorin and benzoylpaeoniflorin were employed to study synchronous release of the optimal formulation. Results: The membrane weight, and the content of PEG 400,and diethyl phthalate( DEP) were the main factors influencing the behavior of TGP release. The accumulated release of the prepared osmotic pump release tablets achieved about 90%. Three main components achieved the desired zero-order release profile and had a synchronized release behavior. Conclusion: The prepared porosity osmotic pump tablets of TGP can achieve the behavior of synchronized release of multi-components with good reproducibility.
Subject(s)
Paeonia , Bridged-Ring Compounds , Delayed-Action Preparations , Glucosides , Monoterpenes , Osmosis , Polyethylene Glycols , Porosity , Reproducibility of Results , Solubility , TabletsABSTRACT
To improve the bioavailability of 10-hydroxycamptothecin, 10-hydroxycamptothecin solid dispersion(HCPT-SD) and 10-hydroxycamptothecin-phospholipid complex-solid dispersion(HCPT-PC-SD) were prepared, and their solubility and dissolution rate were evaluated in this study. SD rates were administered intragastrically with HCPT-SD or HCPT-PC-SD respectively, then their blood samples were collected at different time intervals. The concentration of HCPT in blood was detected by HPLC method with camptothecin as internal standard, and then its pharmacokinetic parameters were calculated and obtained. The results showed that the Cmax, AUC0-t and AUC0-∞ of both kinds of solid dispersion of HCPT were significantly increased than those of crude drug. The AUC0-t of HCPT-SD was increased by 176.87%, and AUC0-t of HCPT-PC-SD was increased by 254.31% as compared with crude drug. Therefore, the two kinds of solid dispersion of HCPT could significantly enhance the bioavailability of HCPT in SD rates, and the effect of HCPT-PC-SD was more obvious.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacokinetics , Camptothecin/analogs & derivatives , Drugs, Chinese Herbal/pharmacokinetics , Animals , Antineoplastic Agents, Phytogenic/chemistry , Biological Availability , Camptothecin/chemistry , Camptothecin/pharmacokinetics , Drug Carriers/chemistry , Drugs, Chinese Herbal/chemistry , Male , Phospholipids/chemistry , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To prepare monolithic osmotic pump tablet of resveratrol. METHODS: Inclusion technology was adopted to enhance its solubility. The optimal formulation of resveratrol inclusion complex osmotic pump tablets was selected by the single-factor method and orthogonal design. The release in vitro of the optimized formulation was also fitted to different models. RESULTS: The tablets with optimized formulation achieved the desired zero-order release profile in 12 h (r = 0.9963) with the cumulative release over 90%. CONCLUSION: Resveratrol can be prepared into monolithic osmotic pump tablets based on the intermediate of inclusion technology, which have obvious characteristic of zero release.
