Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have suggested that the functional polymorphisms in the promoters of matrix metalloproteinases (MMP) genes were associated with the risk of cancers, but no study has ever explored these polymorphisms as risk factors for hepatocellular carcinoma. Recently, we firstly examined whether seven functional polymorphisms in the promoters of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, and MMP-13 have any bearing on the risk of hepatocellular carcinoma, but we found none. In this study, we focused on an additional six MMP polymorphisms, including four functional polymorphisms in the promoters of MMP-7 (A-181G and C-153T) and MMP-8 (C-799T and A-381G), and two nonsynonymous polymorphisms in MMP-10 (A180G) and MMP-21 (C572T). With the polymorphism validation, we found that only MMP-7 A-181G, MMP-8 C-799T, and MMP-21 C572T were polymorphic. These three polymorphisms were then genotyped in 434 patients with hepatocellular carcinoma and 480 controls by PRC-RFLP analysis. The associations between the polymorphisms and hepatocellular carcinoma risk were evaluated while controlling for confounding factors. No significant association with the risk of hepatocellular carcinoma was observed with the three polymorphisms in the overall sample, hepatitis B virus carriers, and non-hepatitis B virus carriers after correction for multiple comparisons. Furthermore, when the analyses were stratified by age, sex, status of smoking and drinking, pack-years of smoking, and family history of hepatocellular carcinoma, there was also no significant association between these polymorphisms and hepatocellular carcinoma risk. Our findings suggest that the polymorphisms MMP-7 A-181G, MMP-8 C-799T, and MMP-21 C572T may not play a major role in mediating susceptibility to hepatocellular carcinoma.
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PMID:No association of MMP-7, MMP-8, and MMP-21 polymorphisms with the risk of hepatocellular carcinoma in a Chinese population. 1876 25

Numerous studies have shown that the levels of matrix metalloproteinase (MMP)-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. This study investigated the effects of caffeic acid phenethyl ester (CAPE), a chemopreventive phytochemical derived from honeybee propolis, on the invasive phenotype of SK-Hep1 human hepatocellular carcinoma cells (SK-Hep1 cells). CAPE effectively suppressed SK-Hep1 cell invasion in a dose-dependent manner. The constitutive expression of MMP-2 and MMP-9 in SK-Hep1 cells was almost completely abolished by treatment with 12.5 muM CAPE. CAPE also significantly inhibited nuclear factor kappa B (NF-kappaB) DNA-binding activity in SK-Hep1 cells. These results taken together suggest that CAPE exerts antimetastatic potential through inhibition of MMP-2 and MMP-9 expression, possibly by targeting NF-kappaB in hepatocellular carcinoma.
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PMID:Caffeic acid phenethyl ester inhibits invasion and expression of matrix metalloproteinase in SK-Hep1 human hepatocellular carcinoma cells by targeting nuclear factor kappa B. 1885 Feb 24

CD147 is reported to be correlated with the malignancy of some cancers, and its overexpression affects the progression of tumor. In the present study, we investigated the function of HAb18G/CD147, a member of CD147 family, on hepatocellular carcinoma (HCC) adhesion, invasion and metastasis in 3-dimensional (3-D) cell co-culture model. The results showed that the extracellular microenvironment could determine the cellular phenotypes and then affected the cellular functions. The expressions of HAb18G/CD147 in HCC cells and fibroblasts were both obviously elevated in 3-D co-culture model. The overexpression of HAb18G/CD147 increased MMPs' (MMP-2 and MMP-9) production (P < 0.01), and was obviously accompanied with enhanced expressions of paxillin, FAK and p-FAK in 3-D cell co-culture model. All the results suggest that HAb18G/CD147 plays an important role in HCC adhesion, invasion and metastasis mainly via modulating synthesis of MMPs and activating integrin signal pathways in fibroblasts and tumor cells themselves under the 3-D co-culture conditions.
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PMID:Enhanced expression of Hab18g/CD147 and activation of integrin pathway in HCC cells under 3-D co-culture conditions. 1905 91

Metastasis is considered to be the major cause of death in patients with cancers, and hepatocellular carcinoma (HCC) is a highly metastatic cancer. Ganoderma lucidum , a well-known mushroom with various biological effects, is a functional food known to contain lucidenic acid. The objectives of this study were to investigate the anti-invasion effect of a lucidenic acid-rich G. lucidum extract (GLE) on human hepatoma HepG2 cells as well as the antiproliferative and antimetastatic effects of GLE in human hepatoma cells implanted into ICR-nu/nu mice. Phorbol-12-myristate-13-acetate (PMA)-induced invasion and matrix metalloproteinase (MMP)-9 expression levels of HepG2 cells were reduced by GLE treatment in a dose-dependent manner. The inhibitory effects of GLE on MMP-9 expression proceeded by inhibiting the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and protein kinase B in the cytosol as well as reducing activator protein-1 and nuclear factor-kappa B levels in the nucleus of HepG2 cells. In a human tumor xenograft model, a dose-response inhibition was observed in the average size, volume, and weight of tumors upon oral administration of GLE. The number of metastatic tumor-bearing mice, the number of affected organs, and the number of tumor foci as well as the MMP-2 and -9 activities in serum of mice were also significantly suppressed by oral administration of GLE. These results suggest that the lucidenic acid-rich GLE could serve as a chemopreventive agent for the tumorigenesis and metastasis of highly invasive hepatoma cells.
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PMID:Inhibitory effects of ganoderma lucidum on tumorigenesis and metastasis of human hepatoma cells in cells and animal models. 1942 27

Morin--a bioflavonoid is a naturally available dietary agent believed to impede cancer promotion and progression. The present study was conducted to decipher, in vivo, the role of morin on the expression of matrix metalloproteinases, cyclooxygenase (COX)-2 and nuclear factor kappa B (NF-kappaB)-p65 during diethylnitrosamine (DEN)-induced hepatocarcinogenesis in Wistar albino rats. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that administration of DEN (200 mg/kg bodyweight in drinking water) to experimental animals caused inflammation of the liver due to up-regulation of NF-kappaB-p65 and COX-2. RT-PCR and immunoblot analysis also revealed that the oral supplementation of morin (500 ppm in diet) to DEN-induced hepatocellular carcinoma rats down-regulated the expression of COX-2 and NF-kappaB-p65, thereby preventing inflammation and angiogenesis mediated hepatocellular carcinogenesis. Further, immunohistological analysis for NF-kappaB-p65 nuclear localization confirms the above observations. Gelatin zymography was performed for matrix metalloproteinase MMP-2 and MMP-9 expression to confirm their role in angiogenesis in DEN induced hepatocellular carcinoma and its modulation by morin. Both MMP-2 and MMP-9 levels were found to be increased in DEN-induced animals when compared to control. MMP-2 and MMP-9 levels were down-regulated in morin post-treated animals when compared to DEN-induced animals favouring prevention of angiogenesis. In conclusion, our findings indicate that morin possessed anti-inflammatory and anti-cancer properties favouring suppression of DEN-induced hepatocellular carcinoma.
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PMID:Morin regulates the expression of NF-kappaB-p65, COX-2 and matrix metalloproteinases in diethylnitrosamine induced rat hepatocellular carcinoma. 1953 2

We investigated anti-invasive effects of the anthocyanins from fruits of Vitis coignetiae Pulliat (known as meoru in Korea) on human hepatoma Hep3B cells. The anthocyanins inhibited cell invasion in a dose-dependent manner as measured by Matrigel (BD Biosciences, San Jose, CA, USA) invasion assays. They also inhibited expression of matrix metalloproteinase (MMP)-2 and MMP-9 and activation of nuclear factor kappaB (NF-kappaB) stimulated by tumor necrosis factor alpha. Taken together, the results of this study indicate that the anthocyanins isolated from fruits of V. coignetiae Pulliat have anti-invasive effects on human hepatoma Hep3B cells and inhibit MMP-2 and MMP-9 gene expression at least in part through the inhibition of NF-kappaB activation.
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PMID:Anti-invasive activity of anthocyanins isolated from Vitis coignetiae in human hepatocarcinoma cells. 1985 58

Hepatocellular carcinoma (HCC) is an aggressive cancer with a dismal outcome largely due to metastasis and postsurgical recurrence. Thus, the inhibition of invasion and metastasis is of great importance in its therapies. Medicinal plants or ethnopharmacology used in folklore medicine continue to be an important source of discovery and development of novel or potential therapeutic agents for treatment of cancer. Chrysanthemum indicum, one of the medicinal plants or ethnopharmacology, is being used for treatment of many diseases including cancer. However, this plant molecular mechanisms underlining the anti-metastatic effects have not been well documented. In this study, Chrysanthemum indicum ethanolic extract (CIE) significantly suppressed proliferation and invasion of MHCC97H cells, one of the HCC cell lines with high metastatic potential, in a dose-dependent manner. CIE markedly decreased MMP-2 and MMP-9 expression, increased simultaneously TIMP-1, and TIMP-2 expression further restoring their balance in the cancer cells. The present study indicates that CIE reduced MHCC97H cell metastatic capability, in part at least, through decrease of the MMP expression, simultaneous increase of the TIMP expression, further restoring their balance as therapeutic target in HCC. It is suggested that Chrysanthemum indicum is a potential novel therapeutic medicinal plant for treatment of HCC or cancer invasion and metastasis.
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PMID:Chrysanthemum indicum ethanolic extract inhibits invasion of hepatocellular carcinoma via regulation of MMP/TIMP balance as therapeutic target. 2004 2

HAb18G/CD147, a member of the immunoglobulin family enriched on the surface of tumor cells, is reported to be correlated with invasion, metastasis, growth, and survival of malignant cells. Here, we found that annexin II, a 36-kDa Ca(2+)- and phospholipid-binding protein and in vivo substrate for tyrosine kinase and PKC, is a new interaction protein of HAb18G/CD147 in human hepatocellular carcinoma (HCC) cells. In the present study, we explored the unclear role of annxin II in HCC invasion and migration and the interaction effects between HAb18G/CD147 and annexin II. Our data show that downregulation of annexin II in HCC cells significantly decreased the secretion of MMP, migration ability, and invasive potential, and affected the cytoskeleton rearrangement of tumor cells. The MMP-2 level and invasive potential of HCC cells were regulated by both annexin II and HAb18G/CD147. Also, interaction effects exist between the two molecules in tumor progression, including MMP-2 production, migration, and invasion. These results suggest that annexin II promotes the invasion and migration of HCC cells in vitro, and annexin II and HAb18G/CD147 interact with each other in the same signal transduction pathway working as a functional complex in tumor progression.
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PMID:Annexin II promotes invasion and migration of human hepatocellular carcinoma cells in vitro via its interaction with HAb18G/CD147. 2004 91

Cancer metastasis is a complex multi-step process, responsible for a majority of cancer-related deaths by affecting the critical organs and causing complications in therapies. Hepatocellular carcinoma is a multi-factorial disease and is the third most common cause of cancer related mortality worldwide. Clinical and experimental studies have shown that MMP-2 and MMP-9 are involved in tumor invasion and metastases and their elevated expression has been associated with poor prognosis. Our recent studies showed a strong anti-oxidant and hepatoprotective effects of bacoside A (BA) against carcinogen. Nevertheless the effect of BA on the activities and expression of MMP-2 and MMP-9 during hepatocellular carcinoma is not yet recognized. Therefore, the present study was designed to assess the same. Results of gelatin zymography study showed that BA co-treatment significantly decreased the activities of MMP-2 and MMP-9, which is increased during hepatocellular carcinoma. Further immunoblot analysis showed decreased expression of MMP-2 and MMP-9 in rats co-treated with BA compared to DEN-induced hepatocellular carcinoma. Our results reveal that BA exerts its anti-metastatic effect against DEN-induced hepatocellular carcinoma by inhibiting the activities and expressions of MMP-2 and MMP-9.
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PMID:Bacoside A downregulates matrix metalloproteinases 2 and 9 in DEN-induced hepatocellular carcinoma. 2008 75

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is also highly metastatic. Metastasis is considered to be the major cause of death in cancer patients. Resveratrol (3,5,4'-trihydroxystilbene) and related analogues have been reported as candidates to prevent cancer growth and invasion. The bioactivity of resveratrol-related analogues could be altered due to the presence and positioning of methoxy groups on the basic resveratrol chemical structure. This study investigated the effects and mechanism of action of resveratrol and its methoxy analogues on invasion of human hepatocarcinoma cells. The migratory and invasive abilities of phorbol 12-myristate 13-acetate (PMA)-treated HepG2 and PMA-untreated Hep3B cells were both reduced in a dose-dependent manner by treatment with resveratrol and 3,5,4'-trimethoxy-trans-stilbene (MR-3). Upon incubation of PMA-treated HepG2 cells with resveratrol (0-50 microM) or MR-3 (0-50 microM), the MMP-9 activity decreased but TIMP-1 protein increased in a dose-dependent manner. With resveratrol (0-50 microM) or MR-3 (0-1 microM) treatment on PMA-untreated Hep3B cells, both of the MMP-9 and MMP-2 activities decreased but TIMP-2 protein increased in a dose-dependent manner. These results suggest that resveratrol and its related methoxy analogue MR-3 might exert anti-invasive activity against hepatoma cells through regulation of MMP-2, MMP-9, TIMP-1, and TIMP-2. Further analysis with semiquantitative RT-PCR showed that the regulation of MMP-9 and TIMP-2 expressions by resveratrol and MR-3 in hepatoma cells may be on the transcriptional level but on the translational or post-translational level for TIMP-1.
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PMID:Evaluation of anti-invasion effect of resveratrol and related methoxy analogues on human hepatocarcinoma cells. 2013 8


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