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1.
Acta Pharmacol Sin ; 42(9): 1507-1515, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33311599

ABSTRACT

Astroglioma is the most common primary tumor in the central nervous system without effective treatment strategies. Temozolomide (TMZ) is a chemotherapeutic drug to treat astroglioma but exhibits low potency and has side effects. Therefore, there is an urgent need to develop new compounds to treat astroglioma. Dalbergia sissoo Roxb was the source of Dalbergia odorifera in traditional Chinese medicine (TCM) and has been clinically used as an anti-tumor medicine. 4-Methoxydalbergione (4MOD) is purified from Dalbergia sissoo Roxb., and shows an inhibitory effect on osteosarcoma, but its effects on astroglioma have not been reported. Here, we evaluate its anti-astroglioma effects on both in vitro and in vivo models. In cultured astroglioma U87 cells, 4MOD inhibited cell proliferation and induced cell apoptosis in a time- and concentration-dependent manner. Compared with TMZ, 4MOD exhibited a tenfold greater potency of anti-astroglioma effects. 4MOD effectively stalled the cell cycle in G2 phase. Transcriptome sequencing (RNA-seq) showed that 4MOD upregulated 158 genes and downregulated 204 genes that are mainly enriched in cell membrane, cell division, cell cycle, p53, TNF, and MAPK signaling pathways, which may underlie its anti-tumor mechanisms. In a nude mouse xenograft model transplanted with U87 cells, 10 mg/kg 4MOD slowed down tumor growth rate, while at 30 mg/kg dose, it reduced tumor size. Collectively, this study demonstrates that 4MOD is a potent native compound that remarkably inhibits U87 astroglioma growth in both in vitro and in vivo models.


Subject(s)
Astrocytoma/drug therapy , Astrocytoma/metabolism , Benzoquinones/pharmacology , Animals , Apoptosis/drug effects , Astrocytoma/genetics , Astrocytoma/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Dalbergia , Drug Resistance, Neoplasm/drug effects , Gene Expression , Heterografts , Humans , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Nude
2.
Anal Bioanal Chem ; 410(29): 7645-7653, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30283999

ABSTRACT

A facile and feasible photoelectrochemical (PEC) immunoassay based on plasmon-enhanced energy transfer between gold nanoparticles (AuNPs) and CdS quantum dots (QDs)/g-C3N4 nanosheets was developed for the ultrasensitive detection of lipoprotein-associated phospholipase A2 (Lp-PLA2). To construct such a sensing platform, the immunosensor was prepared by immobilizing Lp-PLA2 on a CdS QDs/g-C3N4-modified electrode. A competitive-type immunoreaction was utilized for Lp-PLA2 detection, with AuNP-labeled anti-Lp-PLA2 antibody used as the competitor. Introducing AuNPs with the specific antibody for the antigen target Lp-PLA2 led to heavy quenching of the photocurrent of CdS QDs/g-C3N4 due to the plasmon-enhanced energy transfer between AuNPs and CdS QDs. The quenching efficiency decreased with increasing target Lp-PLA2 concentration. Under optimal conditions, the PEC immunosensor presented a good photocurrent response to the target Lp-PLA2 in the dynamic linear range of 0.01-300 ng mL-1, with a low detection limit of 5.3 pg mL-1. Other biomarkers and natural enzymes did not interfere with response of this system. The reproducibility and accuracy of this method for the analysis of human serum specimens were evaluated, and the results given by the method developed here were found to closely correspond to the results obtained with commercial Lp-PLA2 ELISA kits. Importantly, this protocol offers promise for the development of exciton-plasmon interaction-based PEC detection systems. Graphical abstract ᅟ.


Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/chemistry , Cadmium Compounds/chemistry , Gold/chemistry , Light , Metal Nanoparticles/chemistry , Quantum Dots , Sulfides/chemistry , Antibodies, Monoclonal/chemistry , Electrochemical Techniques/methods , Immunoassay/methods , Limit of Detection , Microscopy, Electron, Transmission , Reproducibility of Results
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