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Hepatocellular carcinoma (HCC) is a prevalent and highly malignant cancer throughout the world. Effective treatment of this disease is impeded by the high rate of metastasis, recurrence, and chemoresistance. Recent studies have revealed the close relationship between the malignant phenotype of HCC and cancer stem cells (CSCs). Therefore, CSC-targeted therapy is considered a promising strategy to eradicate HCC. Traditional Chinese medicine (TCM) can be effective in preventing recurrence and metastasis of some advanced HCC. A growing amount of literature has discovered that extracts or compounds derived from TCM exert an anti-CSC effect. This review introduces some formulas and chemical compounds derived from TCMs that have been reported to inhibit CSCs of HCC; these TCM-related drugs may help to provide an alternative approach to help manage cancers, especially for HCC which has a great potential of metastasis, recurrence, and chemoresistance.
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Objective: To explore the pharmacokinetics of self-made gliclazide modified release tablets in Beagle dogs and to evaluate the in vivo and in vitro correlation. Methods: Six Beagle dogs were orally given self-made gliclazide modified release tablets or reference preparation (DaMeiKang) at a dose of 30 mg with self-control cross-over method. Blood samples were collected at different time points after administration. The gliclazide concentration in plasma was determined by high-performance liquid chromatography, and the pharmacokinetic parameters were calculated. The pharmacokinetic characteristics and relative bioavailability of self-made gliclazide modified release tablets were investigated, the bioequivalence was evaluated, and the in vivo and in vitro correlation was calculated. Results: Area under curve (AUC0-∞) of DaMeiKang was (101.74 ± 20.29) μg/(mL · h), and AUC0-∞ of self-made gliclazide modified release tablets was (95.40 ± 28.68) μg/(mL · h). There were no significant differences in the pharmacokinetic parameters between the test and reference formulations (P>0.05). The relative bioavailability of self-made gliclazide modified release tablets was 93.77%, which was bioequivalent with the reference preparation. The in vitro and in vivo correlation analysis showed that the correlation coefficients of DaMeiKang and self-made gliclazide modified release tablets were 0.912 and 0.894, respectively, which were higher than the critical value (r005.7=0.754). The in vitro release rates of the two preparations were correlated with the in vivo absorption rates. Conclusion: The self-made gliclazide modified release tablets have sustained-release characteristics and bioequivalence with reference preparation. The in vivo absorption behavior of gliclazide modified release tablets can be predicted by the in vitro release assay established in this study.
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<p><b>OBJECTIVE</b>To investigate the binding characteristics between an artificial Arg-Gly-Asp (RGD)-containing cyclic peptide [cyclo(CGRGDSPK)] and rat hepatic stellate cells (HSC).</p><p><b>METHODS</b>An artificial RGD-containing cyclic peptide was labeled with fluorescein isothiocyanate (FITC). HSCs were isolated by collagenase in situ liver recirculating and purified by density gradient centrifugation from normal rats. The cells were cultured for 5 days of primary culture (quiescent phenotype) or for 7 days of secondary culture (activated phenotype). To access the binding and uptake, HSCs were incubated with FITC-cRGD of different concentrations at 4 degree C or 37 degree C, and then the binding and uptake were investigated by flow cytometry. The location of FITC-cRGD in HSC was investigated by fluorescent microscopy. Kd and maximal binding sites per cell were calculated by radioligand binding assay (RBA) of receptors using 3H-cRGD. In the interim, FITC-cAGA was used as a peptide control devoid of any binding site.</p><p><b>RESULTS</b>The binding between FITC-cRGD and HSC was saturable, time- and dose-dependent and could compete with overdosed unlabeled cRGD. The fluorescence was mainly distributed in cytoplasma, especially near the nuclei. Kd was 7.05 x 10(-9) mol/L and Bmax per cell was nearly 6.79 x 10(5).</p><p><b>CONCLUSIONS</b>The results demonstrate that cRGD are specifically taken up by HSC through a receptor-mediated pathway. The information is useful for understanding the ligand-receptor interaction of HSC. FITC labeled cyclic RGD-peptides meet the standards of special ligands and FITC does not change the binding activation of cyclic RGD-peptides.</p>
Subject(s)
Animals , Rats , Binding Sites , Cells, Cultured , Hepatocytes , Cell Biology , Metabolism , Oligopeptides , Pharmacology , Peptides, Cyclic , Pharmacology , Protein BindingABSTRACT
Objective To investigate the effects of glycyrrhizin on gene expression of transforming growth factor(TGF)-?signaling pathway of hepatic stellate cell(HSC)in mice by gene microarray tech- nique.Methods The HSCs were isolated from mice and cultured in vitro.Then the mice were divided into control group,TGF-?_1 group(5 ng/ml) or TGF-?_1(5 ng/ml)combined with glycyrrhizin(100?mol/L) group.The cells were collected after 10 hours to extract RNA.A cDNA microarray(GEArray~(TM) Q) targeting TGF-?/BMP signal transduction was used to screen the genes which showed significant changes in expression of TGF-?pathway of HSC by glycyrrhizin.Results The microarray analysis showed that 16 genes(16.7%),such as Smad2,Smad3,Smad7,CoL3A1,CoL1A2,and PAI-1,were upregulated by TGF-?_1 and then down-regulated by glycyrrhizin.Five genes(5.2%)(including BMP7,IGFbp3 and etc.)downregulated by TGF-?_1,were then up-regulated by glycyrrhizin.Finally,2 genes upregulated by TGF-?_1 were then up-regulated predominantly by glycyrrhizin in HSC(T?R2,betaglycan).Changes in some genes,such as Smad2 Smad3,Smad7,were further confirmed to be coincided with cDNA microarray by semi-quantitative RT-PCR.Conclusions The anti-fibrosis mechanisms of glycyrrhizin may be through to interference of TGF-?signaling pathway,decrease the synthesis and increase the degradation of collagen.