الملخص
Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines. Numerous studies have demonstrated a wide range of antitumor activities of chaetocin in vitro and in vivo. Several studies have demonstrated that chaetocin sup?presses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related to tumour initiation and progression, inducing cancer cell apoptosis (intrinsic and extrinsic), enhancing autophagy, inducing cell cycle arrest, as well as inhibiting tumour angiogenesis, invasion and migration. The antitumor effects and molecular mechanisms of chaetocin are reviewed and analysed in this paper, and the prospective applications of chaetocin in cancer prevention and therapy are also discussed. Our review provides the theoretical basis for exploiting the clinical applica?tion of chaetocin in cancer treatment.
الملخص
OBJECTIVE@#To construct a novel non-viral vector loaded with growth and differentiation factor-5 (GDF-5) plasmid using chitosan, hyaluronic acid, and chondroitin sulfate for osteoarthritis (OA) gene therapy.@*METHODS@#Nano-microspheres (NMPs) were prepared by mixing chitosan, hyaluronic acid, and chondroitin sulfate. GDF-5 plasmid was encapsulated in the NMPs through electrostatic adsorption. The basic characteristics of the NMPs were observed, and then they were co-cultured with chondrocytes to observe their effects on extracellular matrix (ECM) protein expression. Finally, NMPs loaded with GDF-5 were injected into the articular cavities of rabbits to observe their therapeutic effects on OA in vivo.@*RESULTS@#NMPs exhibited good physicochemical properties and low cytotoxicity. Their average diameter was (0.61±0.20) μm, and encapsulation efficiency was (38.19±0.36)%. According to Cell Counting Kit-8 (CCK-8) assay, relative cell viability was 75%-99% when the total weight of NMPs was less than 560 μg. Transfection efficiency was (62.0±2.1)% in a liposome group, and (60.0±1.8)% in the NMP group. There was no significant difference between the two groups (P>0.05). Immunohistochemical staining results suggested that NMPs can successfully transfect chondrocytes and stimulate ECM protein expression in vitro. Compared with the control groups, the NMP group significantly promoted the expression of chondrocyte ECM in vivo (P<0.05), as shown by analysis of the biochemical composition of chondrocyte ECM. When NMPs were injected into OA model rabbits, the expression of ECM proteins in chondrocytes was significantly promoted and the progression of OA was slowed down.@*CONCLUSIONS@#Based on these data, we think that these NMPs with excellent physicochemical and biological properties could be promising non-viral vectors for OA gene therapy.