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Sheng-qi Wang

Publications and source records attributed to Sheng-qi Wang.

At least 19 recordsLinked to original sources
PubMed2006

Suppression of tumor growth using antisense oligonucleotide against survivin in an orthotopic transplant model of human hepatocellular carcinoma in nude mice.

Survivin, an inhibitor of apoptosis protein, deserves attention as a selective target for cancer therapy because it is overexpressed in many cancers, including human hepatocellular carcinoma (HCC). Here, we report a novel antisense oligonucleotide (ASO) against survivin for its effectiveness against tumor growth both in vitro and in vivo, and providing evidence in treatment for HCC. Initially, transfection of liver tumor cells HepG2 with ASO resulted in significant cells growth inhibition and reduction expression of survivin mRNA and protein, in a dose-dependent manner. Using caspase-3 protease activation assays, we observed that ASO has induced significantly greater apoptosis rate compared to control oligonucleotides. Furthermore, we used an orthotopic transplant model of HCC in nude mice to investigate the effect of ASO on tumor growth in vivo, and ASO reagents were delivered by intravenous injection. Interestingly, this systemic treatment also resulted in significant inhibition in tumor growth. Tumor growth in mice treated with ASO (50 and 75 mg/kg per day) was significantly inhibited (45.31% and 60.94%, respectively) compared with saline-injected group (p < 0.01), in a dose-dependent manner, and the effect of ASO on tumor growth was associated with downregulation of survivin in tumor xenografts. Moreover, the level of serum alpha-fetoprotein in ASO-treated groups was also decreased in a dose-dependent manner. Taken together, these data suggest that the usefulness of survivin ASO could potentially be a promising gene therapy approach to treatment of HCC.

Animals↗
PubMed2006

[Screening and their anti-tumor activity of antisense oligodeoxynucleotides targeting KDR mRNA in breast cancer MCF-7 cells].

OBJECTIVE: To screen the antisense oligodeoxynucleotides (asONs) which could hybridize with KDR (kinase insert domain-containing receptor) mRNA in an effective and specific way and to explore their anti-tumor effects on breast cancer MCF-7 cell line in vitro. METHODS: The asONs were firstly selected using oligodeoxynucleotides library hybridization or computer prediction, then their hybridization ability with KDR mRNA was further tested with oligonucleotide microarray. The asONs with strong hybridization intensity were selected. Their inhibitory effects on MCF-7 cells proliferation and KDR expression were assayed by MTT, RT-PCR and Western blotting assay, respectively. RESULTS: In 13 asONs selected with oligodeoxynucleotides library hybridization, 8 (8/13, 61.5%) showed strong hybridization signals, while such was only 1 in 17 asONs designed by computer prediction. 9 asONs with strong hybridization intensity were selected and synthesized with phosphorothioated modification. All these asONs inhibited the MCF-7 cells proliferation in a dose-dependent manner, in which asON4 and asON7 screened by oligodeoxynucleotides library in combination with oligonucleotide microarray were the most effective, with inhibitory rates of 51.6% and 62.2% at 0.8 micromol/L, respectively. The KDR expression at mRNA and protein levels was reduced by both the two asONs, in a dose-dependent manner. CONCLUSION: asONs screened by oligodeoxynucleotides library hybridization are well consistent with that chosen with oligonucleotide microarray. The combination of oligodeoxynucleotides library with oligonucleotide microarray is an effective approach of asONs screening. The asONs targeting KDR mRNA showed prominent anti-tumor activity on breast cancer MCF-7 cells.

Breast Neoplasms↗
PubMed2006

[Effects of Siwu Tang on protein expression of HFCL].

OBJECTIVE: To investigate the effects of Siwu Tang on HFCL proliferation and protein expression of bone marrow stromal cells and to discuss molecular mechanism of enriching blood functions of Siwu Tang. METHOD: MTT, flow cytometry and proteomics were used respectively to measure the effect of Siwu Tang on HFCL proliferation, cell cycle and proteinexpression. RESULT: Siwu Tang can promote HFCL proliferation, increase proliferative index, up-regulate 12 kinds of proteins and down-regulate 5 kinds of proteins of HFCL. CONCLUSION: Through promoting HFCL proliferation and acting on multipleprotein targets, the blood enriching function of Siwu Tang was exerted indirectly.

Angelica sinensis↗
PubMed2006

[Effects of fufangdenshen tablets on human atherosclerotic plasma protein using proteomic technique].

OBJECTIVE: To research the effects of fufangdenshen tablets on atherosclerotic plasma protein using proteomic technique and further explore its potential molecular mechanism to cure atherosclerosis. METHOD: The plasma of normal, atherosclerosis and cured group were collected, and the albumin in plasma was removed. Proteomic protocol involved of 2-DE, image analysis and spectrometry detection was used to detect regulated plasma protein by fufangdenshen tablets. RESULT: 3 decreased expressed and 6 higher protein in atherosclerotic plasma could be recovered by fufangdenshen tablets. The levels of fibrinogen, Granzyme C and immunoglobulin were decreased by fufangdenshen tablets. CONCLUSION: The levels of fibrinogen, Granzyme C in atherosclerotic plasma could be decreased by fufangdenshen tablets. The effects of fufangdenshen tablets on atherosclerosis included that: inhibition of adhesion of monocyte, inhibition of proliferation and migration of VSMC, and weakening of inflammation.

Aged↗
PubMed2005

Rapid and reliable detection and identification of GM events using multiplex PCR coupled with oligonucleotide microarray.

To devise a rapid and reliable method for the detection and identification of genetically modified (GM) events, we developed a multiplex polymerase chain reaction (PCR) coupled with a DNA microarray system simultaneously aiming at many targets in a single reaction. The system included probes for screening gene, species reference gene, specific gene, construct-specific gene, event-specific gene, and internal and negative control genes. 18S rRNA was combined with species reference genes as internal controls to assess the efficiency of all reactions and to eliminate false negatives. Two sets of the multiplex PCR system were used to amplify four and five targets, respectively. Eight different structure genes could be detected and identified simultaneously for Roundup Ready soybean in a single microarray. The microarray specificity was validated by its ability to discriminate two GM maizes Bt176 and Bt11. The advantages of this method are its high specificity and greatly reduced false-positives and -negatives. The multiplex PCR coupled with microarray technology presented here is a rapid and reliable tool for the simultaneous detection of GM organism ingredients.

Brassica rapa↗
PubMed2005

Antisense oligodeoxynucleotides targeting the serine/threonine kinase Pim-2 inhibited proliferation of DU-145 cells.

AIM: To investigate the effect of antisense oligodeoxynucleotides (ASODN) targeting Pim-2 on cell proliferation of DU-145 cells. METHODS: Three ASODN targeting Pim-2 were designed and synthesized. After transfection with ASODN, cell proliferation was analyzed using an MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. In addition, Pim-2 mRNA, protein levels, and cell cycles were examined. RESULTS: The ASODN designed and synthesized by our laboratory significantly reduced Pim-2 mRNA level and protein content in DU-145 cells. After transfection with ASODN for 48 h, a marked reduction in cell viability was observed in DU-145 cells in a dose-dependent manner. No remarkable apoptosis occurred in cells treated with ASODN compared with control cells. However, it should be noted that G1 phase arrest was clearly observed in ASODN-treated cells. CONCLUSION: ASODN targeting Pim-2 resulted in a marked reduction in DU-145 cell proliferation, and induction of G1 phase cell cycle arrest is one of the important mechanisms for ASODN to reduce cell growth. Moreover, antisense inhibition of Pim-2 expression provides a new promising therapy target for prostate cancer.

Apoptosis↗
PubMed2005

Inhibition of tumor growth and metastasis with antisense oligonucleotides (Cantide) targeting hTERT in an in situ human hepatocellular carcinoma model.

AIM: To evaluate the in vivo antitumor effects of Cantide and the combined effect with 5-fluorouracil. METHODS: An in situ human hepatocellular carcinoma model was established in mice livers orthotopically. Drugs were administered intravenously and tumor sizes were monitored with calipers. Plasma alpha-fetoprotein(AFP) were detected by radiation immunoassay. Morphology of tumors was evaluated by hematoxylin-eosin (H and E) staining of histological sections. Human telomerase reverse transcriptase (hTERT) protein levels were detected by Western blotting. RESULTS: Cantide significantly inhibit in situ human hepatocellular carcinoma growth in mice with a 75 and 50 mg.kg(-1).d(-1) administration of Cantide compared to the saline group in a dose-dependent manner, which included injecting Cantide 25 mg.kg(-1).d(-1) by iv for 20 d after surgically removing the tumor in liver. Cantide was also found to prevent tumor recurrence in the liver and metastasis in the lung, showing a dose-dependent response. When Cantide was administered by iv combined with 5-fluorouracil, it resulted in a significant reduction in tumor growth compared to either agent alone treatment group. After the treatment with Cantide alone or combined with 5-fluorouracil, plasma AFP concentration decreased in a dose-dependent manner. CONCLUSION: These results demonstrated that Cantide was an effective antitumor antisense oligonucleotide in vivo and has the potential to be developed into a clinical anti-cancer drug.

Animals↗
PubMed2005

[Influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide metabolism using oligonucleotide genotyping microarray].

AIM: To investigate the influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide. METHODS: An oligonucleotide microarray was designed and fabricated to genotype the CYP2C9 accurately and quickly. 137 healthy volunteers were genotyped with the array to investigate the frequency of CYP2C9 functional SNPs. Moreover, 1 homozygous mutant, 9 heterozygous and 10 wild-genotypes subjects in the assay were selected randomly and sequenced directly. After orally taking tolbutamide, blood samples and urine samples were collected, and their pharmacokinetics was studied with HPLC. RESULTS: CYP2C9 *1/*3 were found in 9 of 137 volunteers, CYP2C9 *3/*3 in only one, others were all CYP2C9 *1/*1 wild types. CYP2C9 *2, CYP2C9 *4 and CYP2C9 *5 alleles were not detected. Direct sequencing of the purified PCR products of the heterozygotes, mutant homozygotes and ten wild type individuals gave a corresponding result to that genotyped by microarray. Pharmacokinetic outcome showed that the individuals with CYP2C9 *1/*3 or CYP2C9 *3/*3 had slower metabolic elimination of tolbutamide than those with CYP2C9 *1/*1. CONCLUSION: CYP2C9 genetic polymorphism has a significant influence on the pharmacokinetics of tolbutamide. Pharmacogenomic study will be helpful in guiding rational and individualized medication. Key words: tolbutamide; cytochrom P450 CYP2C9; allele; single nucleotide polymorphism; genotyping

Aryl Hydrocarbon Hydroxylases↗
PubMed2004

Ginsenoside Rg1-induced alterations in gene expression in TNF-alpha stimulated endothelial cells.

BACKGROUND: In China the ginseng root began to be used in medicine over 2000 years ago. Ginsenosides are the most important component isolated from ginseng. The authors investigated the effect of ginsenoside Rg1 on the spectrum of gene expression in the endothelial cells stimulated by TNF-alpha and further explored the potential molecular mechanism of endothelial protection by ginsenoside Rg1. METHODS: Nitric oxide (NO) production in the cultured human umbilical vein endothelial cells (HUVECs) was measured by using an NO assay kit. A home-made oligonucleotide microarray containing approximately 400 cardiovascular disease-related genes was constructed. The alteration of the spectrum of gene expression induced by ginsenoside Rg1 in HUVECs which were activated by TNF-alpha were detected by oligonucleotide microarray analysis. RESULTS: NO production in HUVECs was decreased significantly after TNF-alpha treatment, while pretreatment with ginsenoside Rg1 enhanced NO production in TNF-alphastimulated HUVECs. Ginsenoside Rg1 affected the expression levels of genes involved in vascular constriction, cell adherence, coagulation, cell growth and signal transduction in TNF-alphastimulated HUVECs. CONCLUSIONS: Ginsenoside Rg1 could enhance NO production and the expression of eNOS mRNA in TNF-alpha stimulated HUVECs. Ginsenoside Rg1 regulated sets of genes in endothelial cells and protected endothelial cells from TNF-alpha activation. Microarray analysis provided us with valuable insights into the atheroprotective mechanism by gingsenoside Rg1.

Endothelial Cells↗
PubMed2004

[Effects of siwu tang on protein expression of bone marrow of blood deficiency mice induced by irradiation].

OBJECTIVE: To observe the effects of siwu tang on protein expression of bone marrow of blood deficiency mice and provide the theoretical and experimental basis for understanding the molecular mechanism of blood enriching function of siwu tang. METHOD: Blood deficiency mice were established by using 3.5 Gy 60Co gamma-ray. With proteomic technologies including two-dimensional electrophoresis, image analysis, in-gel digestion, peptide mass fingerprinting and bioinformatics the proteins of bone marrow of blood deficiency mice were isolated, analyzed, and identified. RESULT: Siwu tang could reverse 10 up-regulated and 4 down-regulated proteins of blood deficiency mice bone marrow. Seven of the proteins were likely to be lymphocyte specific protein 1, proteasome 26S ATPase subunit 4, hematopoietic cell protein-tyrosine phosphatase, glyceraldehyde-3-phosphate dehydrogenase, growth factor receptor binding protein 14 and lgals12 respectively. CONCLUSION: Siwu tang can regulate the protein expression of bone marrow of blood deficiency mice and thus promote the growth and differentiation of hematopoietic cells and then exert its effects on blood enriching function.

Adaptor Proteins, Signal Transducing↗
PubMed2004

[Investigation of constituents in siwu tang fractions by chromatographic and ESI-MS methods].

OBJECTIVE: In order to discuss the chemical foundation of hematopoietic effect of Siwu Tang, three fractions of different polarities (C1, C2 and C3) were prepared from Siwu Tang and the characteristics of these fractions' constituents were investigated. METHOD: Fraction C1, C2 and C3 of Siwu Tang and corresponding fractions of Siwu Tang's four ingredient drugs were analyzed and compared, synthetically using the three methods of high-performance thin layer chromatography (HPTLC), high-performance liquid chromatography (HPLC) and direct infusion electrospray ionization mass spectrometry (ESI-MS). RESULT: Fraction C1 of Siwu Tang contained various types of compounds, including ferulic acid, paeoniflorin and supposedly ligustilide, etc. Saccharide content in fraction C1 was very little. The major constituents in fraction C2 of Siwu Tang were paeoniflorin, monosaccaride and disaccharide. The major constituents in fraction C3 of Siwu Tang were monosaccaride and disaccharide. CONCLUSION: With synthetical chromatographic and direct infusion ESI-MS methods, abundant information on composition of fractions of traditional Chinese medicine formulas can be obtained. The results gained with different methods can be compared with each other and corroborate each other, so that the obtained information can be more comprehensive and more definite than that gained with single method. The results of this study are important as references for the discussion of the chemical foundation of hematopoietic effect of Siwu Tang.

Angelica sinensis↗
PubMed2004

[Preliminary study on hematopoietic constituents of si-wu-tang].

OBJECTIVE: To make preliminary study on the chemical foundation of hematopoietic effect of si-wu-tang. METHOD: Si-wu-tang was fractionated by using precipitation method with ethanol and liquid-liquid extraction. Activity was investigated on radiated mice as model of blood deficiency. RESULT: At first si-wu-tang was separated into three fractions, fraction A, B and C. Activity study showed that fraction B and C could raise the amount of peripheral white blood cell in radiated mice. Then fraction B and C were respectively further separated into fraction B1, B2, B3 and fraction C1, C2, C3. Activity study showed that fraction C2, C3 and B3 could raise the amount of peripheral white blood cell in radiated mice. Furthermore, effect of fraction C1, C2, C3, B and paeoniflorin on hematopoietic progenitor cell in bone marrow of radiated mice were investigated. Fraction C2, C3, B and paeoniflorin could promote the proliferation of hematopoietic progenitor cell in bone marrow of radiated mice. CONCLUSION: Fraction C2, C3, B and paeoniflorin are responsible for hematopoietic activity of si-wu-tang.

Angelica sinensis↗
PubMed2003

[Activity of specific deoxyribozymes to cleave hepatitis C virus RNA in vitro].

OBJECTIVE: To analyze the cleavage activity of two deoxyribozymes targeting at hepatitis C virus (HCV) RNA in vitro and evaluate their prospects of antiviral therapy. METHODS: Two specific sequences containing 5' ...A / U... 3' in HCV 5'-noncoding region and 5'-fragment of C region (5'-NCR-C) were selected as the target sites, and with the active region of 5'GGCTAGCTACAACGA3', two phosphorothioate deoxyribozymes (TDRz) named as TDRz-127 and TDRz1 were synthesized. HCV RNA 5'-NCR-C was transcribed in vitro from plasmid pHCV-neo which was completely linearized with restriction endonuclease Nar I, and its 5'-end phosphoric acid was deleted by calf intestinal alkaline phosphatase (CIP), then radiolabelled with T4 polynucleotide kinase and gamma-32P-ATP. Under the conditions such as pH 7.5 and a 10 mmol/L Mg2+ concentration, TDRz-127 and TDRz1 were separately (a 5 micromol/L final concentration) or combinedly (each 2.5 micromol/L) mixed with the substrate RNA (200 nmol/L). After denaturation and then renaturation, the reaction systems were incubated in 37 degrees C, and aliquots were removed to terminate the reaction at intended time points. The cleavage products were separated with 8% denaturated polyacrylamide gel electrophoresis and displayed by autoradiography. Finally, the optical density of each product band was measured with Gel Documentation-Analyzing Systems for calculating the percentages of cleaved HCV 5'-NCR-C. RESULTS: After reaction for 15, 30, 45, 60, 75 and 90 min under the adopted conditions, about 8.3%, 16.1%, 24.3%, 26.2%, 29.4% and 31.1% of HCV 5'-NCR-C was cleaved by TDRz-127 respectively; 7.4%, 13.0%, 15.6%, 18.7%, 19.4% and 20.3% by TDRz1; and 15.1%, 29.6%, 37.8%, 39.1%, 41.5%, 42.6% by combining the two TDRzs. CONCLUSIONS: Cleavage percentage of both TDRz-127 and TDRz1 increases with the time, and the effect of combining the two TDRzs is better than that of anyone.

5' Untranslated Regions↗
PubMed2003

[Antisense oligodeoxynucleotides of human telomerase reverse transcriptase inhibit endometrial carcinoma cell HEC-1A proliferation].

OBJECTIVE: To evaluate antisense technology for human telomerase inhibition in the treatment of endometrial cancer. METHODS: An antisense oligodeoxynucleotides (AODN) directed against the human telomerase transcriptase (hTERT), designed and synthesized to serve as a telomerase inhibitor, was transfected into endometrial carcinoma cell line HEC-1A by lipofectin. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to test the expression of hTERT mRNA and hTERT protein before and after transfection. Telomerase activity was tested by telomeric repeat amplification protocol. The proliferation and growth of HEC-1A were also studied by methyl thiazolyl tetrazolium and cell growth curve before and after transfection. RESULTS: AODN could down-regulate the expression of hTERT mRNA and protein, inhibiting telomerase activity and proliferation of endometrial cancer cell line in a dose- and period-dependent manner. CONCLUSION: Antisense oligodeoxynucleotides of human telomerase transcriptase definitely inhibits the proliferation of endometrial cancer cell line. Telomerase inhibitor may thus become a new gene therapeutic agent for endometrial carcinoma.

Caspases↗