Jian Wang

Tianjin Medical University Cancer Institute and Hospital, T’ien-ching-shih, Tianjin Shi, China

Are you Jian Wang?

Claim your profile

Publications (17)46.02 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CIAPIN1 (cytokine-induced antiapoptotic inhibitor 1) was recently identified as an essential downstream effector of the Ras signaling pathway and has been confirmed to be closely associated with various malignant tumors. However, its potential role in regulating breast cancer metastasis remains unclear. MMPs (matrix metalloproteinases) are a broad family of zinc-biding endopeptidases that participate in the ECM (extracellular matrix) degradation that accompanies cancer cell invasion, metastasis and angiogenesis. In this study, we found up-regulation of CIAPIN1 by lentiviral expression vector inhibited the migration, invasion and MMPs expression of MDA-MB-231 cells. Further, CIAPIN1 over-expression decreased NHE1 (Na(+)/H(+) exchanger 1) expression and ERK1/2 phosphorylation. Importantly, treating CIAPIN1 over-expressed MDA-MB-231 cells with the NHE1 specific inhibitor, Cariporide, further inhibited the metastatic capacity, MMPs expression and phosphorylated ERK1/2. Treatment with the MEK1 specific inhibitor, PD98059, induced nearly the same suppression of CIAPIN1 over-expression-dependent migration, invasion and MMPs expression as was observed with Cariporide. Further, Cariporide and PD98059 synergistically suppressed migration, invasion and MMPs expression of CIAPIN1 over-expressed MDA-MB-231 cells. Thus, our results revealed the mechanism by which CIAPIN1 targeted NHE1 to mediate migration and invasion of MDA-MB-231 cells through regulation of MMPs via ERK1/2 signaling pathway. Copyright © 2015. Published by Elsevier Inc.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is a systemic autoimmune disease and collagen‑induced arthritis (CIA) is an animal model for RA. Micheliolide (MCL) is a novel compound with strong anti‑inflammatory effects. The present study was conducted to evaluate the therapeutic effects of MCL on RA. Mice were randomly divided into four groups and the CIA model mice were treated with methotrexate (MTX), MCL and dimethyl sulfoxide. A score associated with the severity of arthritis was assigned on alternate days from the 22nd day for 60 days. Histopathological changes and the serum levels of cytokines were measured on day 85. The results demonstrated that the MCL treatment group had arthritis scores lower than the CIA group and higher than the MTX group; compared with the CIA group, MCL and MTX significantly reduced the swelling of the paws and suppressed the degeneration of articular cartilage. Expression levels of macrophage colony‑stimulating factor (M‑CSF), tissue inhibitors of metalloproteinases‑1 (TIMP‑1) and complement component 5a (C5/C5a) were lower in the mice with arthritis compared with normal mice, however, following treatment with MCL and MTX, all the mice exhibited significant recovery to differing degrees. Unlike the MTX group, the MCL group failed to recover the level of soluble intercellular adhesion molecule‑1. In addition, the cytokine of B‑lymphocyte chemoattractant (BLC) solely presented in the MCL group. These results suggest that MCL may be considered for use as a novel therapeutic treatment against RA and that changes in the expression of cytokines C5/C5a, TIMP‑1, M‑CSF and BLC may underlie the mechanism by which MCL effects changes in this disease.
    Molecular Medicine Reports 10/2014; 11(1). DOI:10.3892/mmr.2014.2767 · 1.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CIAPIN1 (cytokine-induced antiapoptotic inhibitor 1), was recently identified as an essential downstream effector of the Ras signaling pathway. However, its potential role in regulating myeloid differentiation remains unclear. In this study, we found depletion of CIAPIN1 by shRNAs led to granulocytic differentiation of K562 cells. Meanwhile, the decrease of NHE1 and up-regulation of phosphorylated ERK1/2 were observed after CIAPIN1 depletion. Interestingly, targeted inhibition of NHE1 further promoted the differentiation of K562 cells with CIAPIN1 silencing. Accordingly, ectopic expression of NHE1 reversed this phenotype. Furthermore, ERK1/2 inhibition with the chemical inhibitor, PD98059, abolished CIAPIN1 silencing-induced differentiation of K562 cells after NHE1 inhibition. Thus, our results revealed important mechanism that CIAPIN1 targeted NHE1 to mediate differentiation of K562 cells via ERK1/2 pathway. Our findings implied CIAPIN1 and NHE1 could be new targets in developing therapeutic strategies against leukemia.
    Leukemia Research 09/2014; 38(9). DOI:10.1016/j.leukres.2014.06.013 · 2.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In our previous study, we have found that the tumor multidrug resistance mediated by P-glycoprotein could be reversed by sustained intracellular acidification through down-regulating the multidrug resistance gene 1 mRNA and P-glycoprotein expression. However, the molecular events linking the intracellular acidification and the regulation of P-glycoprotein remain unclear. In the present study, the molecular pathways involved in the regulation of P-glycoprotein expression by the intracellular acidification were investigated. We found that the P-glycoprotein expression was down-regulated by the intracellular acidification through inhibition of p38 mitogen-activated protein kinase (MAPK) and the activation of c-Jun N-terminal kinase (JNK) in the resisitant K562/DOX cells. In the sensitive K562 and HL60 cell lines, the changes of the p38 MAPK expression after the acidification are not as obvious as that of K562/DOX cells, but the activation of extracellular signal-regulated kinase (ERK) is also observed, which indicates that the down-regulation of p38 MAPK by the intracellular acidification might be the resistant cell line specific. Blockade of ERK and JNK signaling by the inhibitors or RNA interference increased p38MAPK activities suggesting that cross-talk within MAPKs is also important for this response. Our study provides the first direct evidence that the reversal of P-glycoprotein-mediated multidrug resistance by intracellular acidification is mediated by the crosstalk of MAPK signaling pathways.
    The International Journal of Biochemistry & Cell Biology 07/2014; 54. DOI:10.1016/j.biocel.2014.06.016 · 4.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic myeloid leukemia is a clonal myeloproliferative disorder disease in which BCR/ABL plays an important role as an oncoprotein and molecular target. Despite the success of targeted therapy using tyrosine kinase inhibitors, CML remains largely incurable, most likely due to the treatment resistance after firstly chemical therapy. So know well the unique molecular pathway of CML is very important. The expressions of CD44 in different leukemia patients and cell lines were detected by real-time PCR and western blotting. The effects of CD44 on proliferation of K562 cells were determined using the MTT and colony formation assays, and even in a nude mouse transplantation model. Then, the cell cycle changes were detected by flow cytometric analysis and the early apoptosis of cells was detected by the annexin V/propidium iodide double-staining assay. The expressions of the cycles and apoptosis-related proteins p21, Cyclin D1 and Bcl-2 were analyzed by western blot and real-time PCR assay. Finally, the decreased nuclear accumulation of beta-catenin was detected by western blotting and immunefluorescence. Firstly, we showed that CD44 expression was increased in several kinds of leukemia patients and K562 cells. By contrast, the down-regulation of CD44 resulted in decreased proliferation with a G0/G1 arrest of cell cycle in K562 cells according to the MTT assay and the flow cytometric analysis. And no significant induction of both the early and late phases of apoptosis was shown by the annexin V-FITC and PI staining. During this process, p21 and cyclin D1 are the major causes for cell cycle arrest. In addition, we found CD44 down-regulation decreased the expression of beta-catenin and increased the expression of phosphorylated beta-catenin. The instability of Wnt/beta-catenin pathway induced by increased expression of p-beta-catenin resulted in a decreased nuclear accumulation in CD44 silenced K562 cells. In the nude mouse transplantation model, we also found the same results. These results show that K562 cells depend to a greater extent on CD44 for proliferation, and CD44 down-regulation may induce a cell cycle arrest through Wnt/beta-catenin pathway. CD44 blockade may be beneficial in therapy of CML.
    Cancer Cell International 11/2013; 13(1):117. DOI:10.1186/1475-2867-13-117 · 1.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The CCAAT/enhancer binding protein homologous protein (CHOP) expression increased when Na(+)/H(+) exchanger 1 (NHE1) was inhibited. Endoplasmic reticulum (ER) stress has been shown to trigger tumor cell death through CHOP. We therefore hypothesized NHE1 activity correlates with ER stress and confers pharmaceutical potential to NHE1 inhibitor as anti-tumor agent. The current study showed that treatment of NHE1 inhibitor Cariporide led to ER stress-induced up-regulation of the DR5 receptor which is mediated by CHOP at transcriptional level. We also determined that ER stress induced JNK activation was responsible for modulation of CHOP. Combining Cariporide with TRAIL led to a significantly enhanced level of apoptosis that was abrogated by siRNA silencing of CHOP. These studies provide a potential mechanistic rationale for the use of NHE1 inhibitor in combination with DR5 agonists to induce apoptosis in leukemia.
    Leukemia & lymphoma 11/2013; DOI:10.3109/10428194.2013.861064 · 2.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CUEDC2, a newly reported protein, has been found to be ubiquitously expressed in human tissues and repress NF-κB activity. To study the role of CUEDC2 in chronic myeloid leukemia (CML), we explored the function of CUEDC2 in CML cells through using the CML cell line K562 and its imatinib resistant cells K562/G01. K562 cells expressed a relatively higher level of CUEDC2 compared to K562/G01 cells. Knockdown of CUEDC2 in K562 cells resulted in decreased cell apoptosis after imatinib treatment; when CUEDC2 was overexpressed in K562/G01 cells, imatinib induced more cell apoptosis. By analyzing the activity of NF-κB, the results indicated a negative association between the expression of CUEDC2 and NF-κB signaling pathway in these CML cells. Our data suggested that the expression level of CUEDC2 has an inverse correlation with imatinib resistance and activity of NF-κB signaling pathway in CML cells, CUEDC2 could regulate imatinib sensitivity in CML cells at least partially through NF-κB signaling pathway.
    Leukemia research 09/2013; DOI:10.1016/j.leukres.2013.08.019 · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and Aims: Recently, genetic association studies have linked a number of single nucleotide polymorphisms (SNPs) with liver fibrosis risk of hepatitis C. The present study was designed to validate the association of emerging SNPs with development of liver cirrhosis and chronicity in a Chinese population infected with hepatitis B virus (HBV). Methods: 714 Chinese subjects with persistent HBV infection (429 with evident liver cirrhosis and 285 without cirrhosis clinically or pathologically) and 280 subjects with spontaneous HBV clearance were studied. Six SNPs in five candidate genes were detected with the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. The distribution of each polymorphism was compared between the age-matched cirrhotic and noncirrhotic subjects, and between subjects with persistent infection and spontaneous HBV clearance. Results: The rs2679757 polymorphism of antizyme inhibitor 1 (AZIN1) gene was associated with the risk of cirrhosis (odds ratio [OR] for GG+AG versus AA=1.47, 95% confidence interval [CI]=1.08-2.01, p=0.01). So was rs886277 in the transient receptor potential cation channel subfamily M, member 5 (TRPM5) gene (OR for CC versus CT+TT=1.63, 95% CI=1.20-2.22, p=0.002). The frequencies of these two SNPs were also associated with the severity of decompensated cirrhosis based on the Child-Pugh classification. Genotype frequencies of other SNPs were not different between the cirrhotic and noncirrhotic groups. No SNPs were associated with the outcome of spontaneous HBV clearance. Conclusions: AZIN1 rs2679757 and TRPM5 rs886277 are associated with the risk of HBV-related liver cirrhosis in Chinese. The emerging SNPs warrant further clinical validation in other cohorts or ethnic groups, and could lead to mechanistic studies to reveal their contributions to fibrosis progression.
    Genetic Testing and Molecular Biomarkers 07/2013; DOI:10.1089/gtmb.2013.0058 · 1.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The effect of hypoxia on the differentiation of chronic myeloid leukaemic K562 cells were studied, as was the role of the NHE1 (Na+/H+ exchanger 1). Hypoxia induced differentiation of K562 cells as seen by modifications in their morphological features, up-regulation of C/EBPα (CCAAT/enhancer-binding protein α), and marked IL-8 (interleukin-8) release. Inhibition of NHE1 under hypoxia additionally enhanced the level of C/EBPα and further promoted leukaemic cells differentiation. Pharmacological inhibition of p38 MAPK (mitogen-activated protein kinase) also significantly suppressed C/EBPα expression under hypoxia conditions after NHE1 inhibition. These results indicate the enhancement of hypoxia-induced K562 differentiation by NHE1 inhibition, which may be due to up-regulation of C/EBPα via p38 MAPK signalling pathway, which suggests a possible therapeutic target of NHE1 under hypoxia microenvironment in the treatment of leukaemic diseases.
    Cell Biology International 04/2012; 36(8):739-45. DOI:10.1042/CBI20100919 · 1.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Na(+) /H(+) exchanger 1 (NHE1), acting as an important regulator of intracellular pH (pH(i) ) and extracellular pH (pH(e) ), has been known to play a key role in the metastasis of many solid tumours. However, the exact mechanism underlying these processes, especially in cervical cancer, is still poorly understood. In the current study, we first showed that the inhibition of NHE1 activity by the specific inhibitor cariporide could suppress migration and invasion of HeLa cells in vitro. Moreover, cariporide also reversed the enhanced migration and invasion in HeLa cells by overexpressed membrane-type 1 matrix metalloproteinase (MT1-MMP). Subsequently, our results showed that NHE1 regulated the expression of MT1-MMP at both messenger RNA and protein levels as well as its localization. Meanwhile, we observed slight modification in the morphology of HeLa cell after treating with cariporide. The present work indicates that NHE1 mediates HeLa cell metastasis via regulating the expression and localization of MT1-MMP and provides a theoretical basis for the development of novel therapeutic strategies targeting cervical cancer. Copyright © 2011 John Wiley & Sons, Ltd.
    Cell Biochemistry and Function 01/2012; 30(1). DOI:10.1002/cbf.1815 · 2.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancer is a leading cause of morbidity in women worldwide. neutrophil gelatinase-associated lipocalin (NGAL), a useful biomarker of ER negative (ER(-)) breast cancer, promotes local tumor invasion and lymph node metastasis. We first identified the distinctive expression of NGAL in two breast cancer cell lines MCF7 and MDA-MB-231 cells, and then confirmed NGAL as a critical inducer of metastasis. Finally, the transcriptional factor CCAAT enhancer-binding proteins ζ (C/EBP ζ) was overexpressed in MDA-MB-231 cells. Consistent with the effect of NGAL knockdown, C/EBP ζ overexpression caused the significant changes that could prevent cell metastasis. C/EBP ζ overexpression induced a strong decrease in NGAL and matrix metalloproteinases (MMPs) expressions as determined by quantitative real time PCR and Western blotting. To identify the potential role of C/EBP ζ on regulating of NGAL in breast cancer, we established the dual-luciferase reporter assay for NGAL in MDA-MB-231 cells cotransfected with C/EBP ζ. Promoter reporter assays determined that C/EBP ζ directly repressed the human NGAL gene promoter activity by inhibiting the NGAL transcription. Taken together, this work identified that the C/EBP ζ overexpression downregulated NGAL to inhibit migration and invasion of breast cancer, which could be used as a novel strategy for breast cancer therapy.
    Biochimica et Biophysica Acta 10/2011; 1813(10):1803-13. DOI:10.1016/j.bbamcr.2011.06.010 · 4.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The key factors in the pathogenesis of liver fibrosis are the activation and proliferation of hepatic stellate cells (HSCs), which express integrin αvβ3 after activation. This study aimed to explore the potential of (99m)Tc-labeled cyclic arginine-glycine-aspartic acid pentapeptide (cRGD) as a single photon emission computed tomography (SPECT) radiotracer to image hepatic integrin αvβ3 expression to reflect HSC activity in fibrotic livers. Rat models of liver fibrosis caused by thioacetamide or carbon tetrachloride (CCl(4)) treatment were employed to examine the expression and distribution of integrin αvβ3 during fibrotic progression or regression. The binding activity of radiolabeled cRGD to integrin αvβ3 was assessed in liver sections. SPECT was performed to determine hepatic integrin αvβ3 expression in rats with different stages of liver fibrosis. Protein and messenger RNA (mRNA) levels of integrin αv and β3 subunits were increased with the progression of liver fibrosis and reduced with its regression. The cell type that expressed the majority of integrin αvβ3 in fibrotic livers was found to be activated HSCs. The cRGD binding to activated HSCs displayed a high receptor-coupling affinity and an abundant receptor capacity. Iodine-125 ((125)I)-labeled cRGD bound to fibrotic liver sections and the binding activity was the highest in advanced fibrosis. Intravenously administered carboxyfluorescein-labeled cRGD was accumulated in fibrotic liver, and the accumulation amount was increased with the progression and reduced with the regression of fibrosis. A SPECT imaging study with (99m)Tc-labeled cRGD as a tracer demonstrated that the radioactivity ratio of liver to heart increased progressively along with severity of hepatic fibrosis. Conclusion: Hepatic integrin αvβ3 expression in fibrotic liver reflects HSC activity and its imaging using (99m)Tc-labeled cRGD as a SPECT radiotracer may distinguish different stages of liver fibrosis in rats.
    Hepatology 09/2011; 54(3):1020-30. DOI:10.1002/hep.24467 · 11.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the effect of inhibition of Na(+)/H(+) exchanger isoform1 (NHE1) on K562 leukemia-driven angiogenesis, the selective NHE1 inhibitor cariporide was used. Cariporide treatment of K562 resulted in a decrease in pHi and down-regulation of VEGF secretion. The proliferation, migration and in vitro tube formation of human umbilical vein endothelial cells was decreased in cariporide treated K562 condition medium (CM) while VEGF supplement could partially restore the inhibitory effect. Subcutaneous injection of nude mice with cariporide inhibited K562 tumor growth with a reduction of the density of microvessels compared to the control group.
    Leukemia research 07/2011; 35(11):1506-11. DOI:10.1016/j.leukres.2011.07.001 · 2.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Na⁺/H⁺ exchanger 1 (NHE1), an important regulator of intracellular pH (pH(i)) and extracellular pH (pH(e)), has been shown to play a key role in breast cancer metastasis. However, the exact mechanism by which NHE1 mediates breast cancer metastasis is not yet well known. We showed here that inhibition of NHE1 activity, with specific inhibitor Cariporide, could suppress MDA-MB-231 cells invasion as well as the activity and expression of MT1-MMP. Overexpression of MT1-MMP resulted in a distinguished increase in MDA-MB-231 cells invasiveness, but treatment with Cariporide reversed the MT1-MMP-mediated enhanced invasiveness. To explore the role of MAPK signaling pathways in NHE1-mediated breast cancer metastasis, we compared the difference of constitutively phosphorylated ERK1/2, p38 MAPK and JNK in non-invasive MCF-7 cells and invasive MDA-MB-231 cells. Interestingly, we found that the phosphorylation levels of ERK1/2 and p38 MAPK in MDA-MB-231 cells were higher than in MCF-7 cells, but both MCF-7 cells and MDA-MB-231 cells expressed similar constitutively phosphorylated JNK. Treating MDA-MB-231 cells with Cariporide led to decreased phosphorylation level of both p38 MAPK and ERK1/2 in a time-dependent manner, but JNK activity was not influenced. Supplementation with MAPK inhibitor (MEK inhibitor PD98059, p38 MAPK inhibitor SB203580 and JNK inhibitor SP600125) or Cariporide all exhibited significant depression of MDA-MB-231 cells invasion and MT1-MMP expression. Furthermore, we co-treated MDA-MB-231 cells with MAPK inhibitor and Cariporide. The result showed that Cariporide synergistically suppressed invasion and MT1-MMP expression with MEK inhibitor and p38 MAPK inhibitor, but not be synergistic with the JNK inhibitor. These findings suggest that NHE1 mediates MDA-MB-231 cells invasion partly through regulating MT1-MMP in ERK1/2 and p38 MAPK signaling pathways dependent manner.
    Experimental Cell Research 06/2011; 317(14):2031-40. DOI:10.1016/j.yexcr.2011.05.026 · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A cirrhosis risk score (CRS) comprised of single nucleotide polymorphisms (SNPs) in seven genes that predicts the risk of cirrhosis in Caucasian hepatitis C has been reported. The present study was to evaluate the association of 11 separate but related SNPs and the CRS with cirrhosis risk in Chinese hepatitis B patients. A total of 563 Chinese subjects with persistent HBV infection (349 with evident liver cirrhosis and 214 without cirrhosis clinically or pathologically) were studied. The candidate SNPs were detected with a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. The allele frequency and genotype distribution of each polymorphism as well as the CRS value within the cirrhosis and non-cirrhosis subjects were compared. The rs2679757 polymorphism of the antizyme inhibitor 1 (AZIN1) gene was associated with the risk of cirrhosis (x2 = 6.79, P = 0.03, odds ratio for GG+AG versus AA = 1.63, 95% confidence interval = 1.13-2.35). A gene variant (rs886277) in the transient receptor potential cation channel subfamily M, member 5 gene (TRPM5) was associated with liver cirrhosis, but did not reach statistical significance (x2 = 5.77, P = 0.06). Two SNPs (rs4986791, rs62522600) are not polymorphic in Chinese. Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups. The overall CRS values were not different between the cirrhotic and non-cirrhotic groups (median value 0.57 versus 0.62, Z = -1.05, P = 0.29). SNP rs2679757 in the AZIN1 gene is associated with the risk of HBV-related liver cirrhosis in Chinese. The CRS for Caucasian population has limited applicability for predicting liver cirrhosis in Chinese hepatitis B patients. SNPs associated with cirrhosis prognosis in hepatitis B patients and liver diseases with other etiologies warrant further clinical validation.
    Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 03/2011; 19(3):169-73.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Targeting hepatic stellate cells (HSCs) has been challenging due to the lack of specific receptors or motifs on the cells. The aim of the present study was to develop a HSC-specific system for improving drug delivery to HSCs. The affinity of a cyclic peptide containing Arg-Gly-Asp (cRGD) to collagen type VI receptor on HSCs was examined in both in vitro and in vivo experiments. Sterically stable liposomes (SSLs) were modified with this peptide to yield a new carrier, cRGD-SSL. The targeting efficiency of this carrier in delivering interferon (IFN)-alpha1b was investigated in a rat model of liver fibrosis induced by bile duct ligation (BDL). When incubating HSCs or hepatocytes with cyclic RGD peptide, the peptide was bound preferentially to activated HSCs. Biodistribution study showed that the accumulation of cRGD peptide-labeled liposomes in HSCs isolated from BDL rats was 10-fold more than unlabeled SSLs. BDL rats receiving injections of IFN-alpha1b entrapped in cRGD-SSL exhibited significantly reduced extent of liver fibrosis compared with BDL control rats or BDL rats treated with IFN-alpha1b entrapped in SSLs. Thus, cRGD-SSL is an efficient drug carrier, which selectively targets activated HSCs and improves drug therapy for liver fibrosis to a significant extent. This liposomal formulation represents a new means of targeting drug carrier for the treatment of liver fibrosis, and it may have potential clinical applications.
    Journal of Pharmacology and Experimental Therapeutics 09/2007; 322(2):560-8. DOI:10.1124/jpet.107.122481 · 3.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the antifibrotic effect of receptor-mediated sterical stability liposome (SSL) targeting hepatic stellate cells (HSCs) and containing recombinant human interferon-alpha 1b (IFNalpha-1b) on hepatic cirrhosis. The ligand, cyclo (RGD) with specific affinity to HSCs, was incorporated via PEG into the lipid bilayers of SSL. Forty male SD rats were randomly divided into 4 equal groups: liver fibrosis model group undergoing double ligation and cutting of the common bile duct (BDL group), BDL + IFN-SSL group, undergoing BDL and injection of IFN 50,000 IU per week via caudal vein for 4 times; IFN-RGD-SSL treatment group, undergoing BDL and injection of IFN-RGD-SSL (equal to 50,000 IU per week) via caudal vein for 4 times; and sham operation group used as control. The rats were killed 24 hours after the last injection. Their livers and serum samples were collected. Pathological changes of the liver were observed with HE and alpha-SMA immunohistochemical staining. Biochemical automatic analyzer was used to test the serum indices of liver function: ALT, AST, total bilirubin (TBIL), alkaline phosphatase, and gamma-glutamine (gamma-GT). Radioimmunoassay method was used to examine the s serum index of liver fibrosis: HA, procollagen III (PCIII), LN, and CIV. Colorimetry was used to examine the level of hydroxyl proline (Hyp). RT-PCR was used to detect the mRNA expression of type I collagen. Western blotting was used to examine the protein expression of alpha-SMA of HSC. Compared with the control group, liver fibrosis was seen in the other 3 groups, especially in the BDL group. In comparison with the sham operation group, the levels of serum indices of liver fibrosis, liver hydroxyl proline content, and expression of type I collagen mRNA and alpha-SMA protein in liver were significantly higher in the other groups (all P < 0.05), being significantly lower in the BDL + IFN-RGD-SSL group than in the BDL + IFN-SSL group (all P < 0.05). The receptor-mediated IFN-RGD-SSL displays good targeting antifibrotic effects on liver fibrosis.
    Zhonghua yi xue za zhi 04/2005; 85(15):1015-20.

Publication Stats

94 Citations
46.02 Total Impact Points

Institutions

  • 2015
    • Tianjin Medical University Cancer Institute and Hospital
      T’ien-ching-shih, Tianjin Shi, China
  • 2011
    • Peking Union Medical College Hospital
      Peping, Beijing, China
  • 2005
    • Fudan University
      Shanghai, Shanghai Shi, China