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1.
Mol Med Rep ; 13(5): 3929-35, 2016 May.
Article in English | MEDLINE | ID: mdl-26986232

ABSTRACT

Aberrant microRNA (miRNA or miR) expression has been reported to contribute to the pathogenesis of hepatocellular carcinoma (HCC). However, the involvement of specific miRNAs in HCC remains to be elucidated. The present study aimed to investigate the potential role of miR-200b and the mechanism underlying its function in hepatocarcinogenesis. The results of the present study demonstrated that the expression levels of miR­200b were significantly reduced in HCC tissue samples, as compared with normal liver (NL) and para­tumorous (PT) tissue samples. The results also revealed that miR­200b expression levels in HepG2 cells were significantly decreased compared with those in L02 cells. In addition, western blotting and reverse transcription­quantitative polymerase chain reaction demonstrated that the expression levels of DNA methyltransferase 3a (DNMT3a), a possible target gene for miR­200b, were significantly higher in HCC tissue samples, as compared with those in NL and PT tissue samples. Furthermore, the data suggested that DNMT3a was a direct target gene of miR­200b. Upregulated miR­200b expression in HepG2 cells led to a decrease in DNMT3a expression levels, and an inhibition of cell proliferation. These results suggested that miR­200b has an important role in hepatocarcinogenesis and acts by downregulating DNMT3a expression. Thus, miR-200b may be a promising target for HCC treatment.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Cell Proliferation , DNA (Cytosine-5-)-Methyltransferases/biosynthesis , Gene Expression Regulation, Neoplastic , Liver Neoplasms/metabolism , MicroRNAs/biosynthesis , Neoplasm Proteins/biosynthesis , RNA, Neoplasm/biosynthesis , Adult , Aged , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Methyltransferase 3A , Female , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , MicroRNAs/genetics , Middle Aged , Neoplasm Proteins/genetics , RNA, Neoplasm/genetics
2.
Acta Pharmaceutica Sinica ; (12): 927-931, 2014.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-244993

ABSTRACT

This is to report the screening, extracting and validating antitumor components and compounds from Stellera chamaejasme L. under the case of discrete distribution of active data. In this work, different components from Stellera chamaejasme L. were collected by HPD macroporous resin and polyamide resin column, and their antitumor activity on A549 were tested by MTT assay. Activity results indicate that activity of components at 30-39 min is more potent than that of Stellera chamaejasme L. extract, and the activity of components at 33.97 min is equivalent to positive drug, cis-platinum at 100 microg x mL(-1), but with totally different mode of action. Under the case of discrete activity, the weight analysis is capable of screening active components and compounds from natural products.


Subject(s)
Humans , Antineoplastic Agents, Phytogenic , Pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Thymelaeaceae , Chemistry
3.
Acta Pharmaceutica Sinica ; (12): 911-916, 2013.
Article in English | WPRIM (Western Pacific) | ID: wpr-259530

ABSTRACT

Z-Ligustilide, a major phthalide isolated from a widely used traditional Chinese medicine Ligusticum chuanxiong, possesses various pharmacological activities including neuroprotective, anti-inflammatory, antiproliferative and vasorelaxing effects. However, it is unstable and inclined to degrade in natural conditions, which limits its study and application greatly. In this study, degradation behavior of Z-ligustilide and its degradation products stored at room temperature under direct sunlight were investigated and structure elucidated by HPLC-UV, UPLC-QTOF-MS and NMR. Z-ligustilide degradation and total five degradation products were generated and detected. Two degradation products were unequivocally identified as senkyunolide I and senkyunolide H by comparison with reference compounds. Another two degradation products were further isolated by semi-preparative HPLC and structure elucidated as (E)-6, 7-trans-dihydroxyligustilide and (Z)-6, 7-epoxyligustilide by 1H and 13C NMR, respectively. The degradation pathways of Z-ligustilide were finally proposed. Oxidation, hydrolysis and isomerization are the major degradation reactions.


Subject(s)
4-Butyrolactone , Metabolism , Benzofurans , Metabolism , Chromatography, High Pressure Liquid , Hydrolysis , Ligusticum , Chemistry , Magnetic Resonance Spectroscopy , Metabolic Networks and Pathways , Oxidation-Reduction , Plant Roots , Chemistry , Plants, Medicinal , Chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-346890

ABSTRACT

<p><b>OBJECTIVE</b>To analyze and identify the chemical constituents in rat brain tissues after oral administration of Chuanxiong Rhizoma extracts.</p><p><b>METHOD</b>The dosed and blank rat brain tissues were analyzed by UPLC-Q-TOF-MS. Different peaks were observed in total ion chromatograms and then identified according to their retention time, accurate mass weight, MS and MS/MS data.</p><p><b>RESULT</b>After oral administration of Chuanxiong Rhizoma extracts, 3 compounds were absorbed into rat brain tissues through BBB. They were identified as senkyunolide I, senkyunolide A and ligustilide.</p><p><b>CONCLUSION</b>The study is helpful for interpreting effective substance of Ligusticum chuanxiong.</p>


Subject(s)
Animals , Female , Humans , Rats , Brain , Metabolism , Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Pharmacokinetics , Ligusticum , Chemistry , Mass Spectrometry , Methods , Rats, Sprague-Dawley , Rhizome , Chemistry
5.
Zhonghua Gan Zang Bing Za Zhi ; 10(5): 366-9, 2002 Oct.
Article in Chinese | MEDLINE | ID: mdl-12392620

ABSTRACT

OBJECTIVE: To determine the relation between the vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), and microvessel density (MVD) as well as the influence on portal vein thrombosis and transfer (PVTT) in hepatocellular carcinoma (HCC). METHODS: Tumor specimens were collected in 36 patients (16 patients with PVTT, the other patients without PVTT and metastasis) undergoing resection of HCC and thrombectomy. PVTT specimens of 16 patients were named Group A1, and HCC of the same patients named Group A2. The other 20 patients belonged to Group B. In situ hybridization and immunohistochemistry were used to investigate VEGF, PCNA expression and MVD. The intensity was evaluated with a computer image analyzer-cell analysis system. RESULTS: VEGF mRNA expression was detected in the tumor cells. The expression rates in Group B, A2, and A1 were 30%, 100%, and 100%, respectively. Group A2 and A1 were higher than Group B (P<0.01). VEGF protein expression was often detected in the tumor cells, vascular endothelial cells, and fibroblast cells. Invasion was detected in the small vein in Group A2, and more tumor cell colony detected in Group A1. The expression rates of VEGF protein in Group B, A2, and A1 were the same as VEGF mRNA. The intensity of VEGF mRNA and protein were all lower in Group A2 than Group A1 (P<0.01). In Group B, A2, and A1, MVD and PCNA-LI were gradually elevated. PCNA reactive vascular endothelial cells were occasionally observed in Group A2, and often observed in Group A1. There was a statistically significant correlation between the intensity of VEGF expression, PCNA-LI and MVD in Group A2 and A1, and significant correlation between PCNA-LI and MVD in Group B, A2, and A1. CONCLUSIONS: Overexpression of VEGF could be an important factor of the high MVD and the highly proliferative activity of cancer cells in HCC and PVTT. High MVD and PCNA-LI associate very well with the formation of PVTT and metastasis in HCC.


Subject(s)
Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/blood supply , Liver Neoplasms/pathology , Microvessels/pathology , Portal Vein/pathology , Venous Thrombosis/pathology , Aged , Cell Proliferation , Humans , Immunohistochemistry , Proliferating Cell Nuclear Antigen , RNA, Messenger , Vascular Endothelial Growth Factor A
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