ABSTRACT
Glioma is the most common neoplasm of the central nervous system, with the highest mortality rate. The present study was designed to examine the therapeutic effect of Iguratimod (IGU) encapsulated-poly (lactic-co-glycolic acid) PLGA nanoparticles (IGU-PLGA-NPs), which showed inhibition of glioma cells proliferation both in vitro and in vivo. IGU encapsulated in PLGA nanoparticles with an average size of 100-200 nm was prepared using modified double-emulsion (W1/O/W2) method. Cell Counting Kit-8 (CCK-8) analysis of Glioma cancer cells and glioma stem-like cells (GSCs) demonstrated significant inhibition of their growth treated with IGU-PLGA-NPs. IGU-PLGA-NPs inhibit migration in glioma cells as well as tumor sphere formation in GSCs. Treatment with IGU-PLGA-NPs showed a significant decrease in tumor growth through the apoptotic pathway in mice model without any visible organ toxicity and it can successfully cross the blood brain barrier (BBB). Most Importantly, IGU-PLGA-NPs significantly depleted growth of U251 Temozolomide-resistant (U251TMZ-R) cells.
Subject(s)
Chromones/therapeutic use , Drug Resistance, Neoplasm , Glioma/drug therapy , Nanoparticles/chemistry , Neoplastic Stem Cells/pathology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Sulfonamides/therapeutic use , Temozolomide/therapeutic use , Animals , Apoptosis/drug effects , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/pathology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Self Renewal/drug effects , Chromones/pharmacology , Drug Resistance, Neoplasm/drug effects , Glioma/pathology , Humans , Male , Mice, Inbred BALB C , Mice, Nude , Neoplastic Stem Cells/drug effects , Spheroids, Cellular/drug effects , Spheroids, Cellular/pathology , Sulfonamides/pharmacology , Temozolomide/pharmacology , Treatment OutcomeABSTRACT
Objective To compare the expression level of miR-92b in SHanG-44 glioma cells and glioma stem cells .Methods The tumor stem cells were screened from the SHG-44 glioma cells and identified by immunofluorescence .Then it was induced to differentiate .The transcription level of miR-92b was determined by RT-PCR and real-time quantitative PCR before and after differ-entiation .Results The miR-92b expression level in differentiated tumor cells was about 3 times higher than in tumor stem cells . Conclusion T he miR-92b gene is involved in the process of differentiation of glioma stem cells .
