UNIPROT:Q99542 - FACTA Search

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Query: UNIPROT:Q99542 (matrix metalloproteinase)
15,999 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic cancer is now one of the most common causes of cancer death worldwide. K-ras mutations are present in up to 90% of pancreatic cancer cases. The expression of mutant K-ras activates the Akt/protein kinase B pathway, resulting in the activation of the nuclear factor-kappaB (NF-kappaB) transcriptional factor. Constitutive NF-kappaB activity plays a key role in pancreatic carcinoma. NF-kappaB has been shown to inhibit apoptosis in response to chemotherapeutic agents. In the present study, the effects of lidamycin (LDM), a member of the enediyne antibiotic family, were investigated on two established pancreatic cell lines, PANC-1 and SW1990. A dose-dependent inhibition of phospho-Akt and NF-kappaB activation was found in the cells treated with LDM as determined by Western blot analysis. Moreover, a down-regulation of K-ras mRNA and a protein expression by LDM were observed in both cell lines as determined by reverse transcription-PCR and Western blot analysis. By MTT assay, a remarkable difference in chemosensitivity to LDM, mitomycin, adriamycin, taxol, and gemcitabine was found in both cell lines. The IC50 values of LDM for the PANC-1 or SW1990 cells were 0.955+/-0.414 or 0.426+/-0.212 nM, respectively, lower than those of the other drugs. Growth inhibition, apoptosis induction and cell cycle arrest were observed in the LDM-treated cells. LDM decreased the invasive potential of pancreatic cancer cells by reducing matrix metalloproteinase-9 activity. Furthermore, LDM was found to suppress the growth of SW1990 xenografts in nude mice. Treatment with an i.v. injection of LDM at the dose of 0.02 and 0.04 mg/kg (once a week for two weeks) inhibited the growth of xenografts by 66 and 72%, respectively. By contrast, an i.p. injection of gemcitabine at the dose of 80 mg/kg inhibited the growth of xenografts by 38%. Our findings suggest that LDM is active in the down-regulation of NF-kappaB and could play a positive role in relevant targeted chemotherapy for pancreatic carcinoma.
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PMID:Down-regulation of the nuclear factor-kappaB by lidamycin in association with inducing apoptosis in human pancreatic cancer cells and inhibiting xenograft growth. 1748 3

Liposarcoma, a malignancy of fat cells, is the most common soft tissue sarcoma. Though rare, poorly differentiated liposarcomas commonly metastasize to lungs and liver, leading to poor prognosis. Prevention of Extracellular matrix (ECM) degradation by inhibition of matrix metalloproteinases (MMPs) activity has been shown to be a promising therapeutic approach to inhibition of cancer progression. A nutrient mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract has shown significant anticancer activity against a number of cancer cell lines. We investigated the effect of NM on liposarcoma cell line SW-872 proliferation (MTT assay), MMP secretion (gelatinase zymography), invasion through Matrigel, and apoptosis and morphology (live green caspase kit and H&E). Liposarcoma cell growth was inhibited by 36 and 61% at 500 and 1,000 microg/ml NM. Zymography demonstrated both MMP-2 and MMP-9 secretion, with PMA-enhanced MMP-9 activity. NM inhibited both MMPs with virtual total inhibition at 500 microg/ml NM. Invasion through Matrigel was inhibited at 100, 500, and 1,000 microg/ml by 44, 75, and 100%, respectively. Dose-dependent apoptosis of liposarcoma cells was evident with NM challenge, with virtually all cells exposed to 1,000 microg/ml NM in late apoptosis. H&E staining did not demonstrate any changes in morphology at lower concentrations. However, some apoptotic changes were evident at higher concentrations. In conclusion, NM significantly inhibited liposarcoma cell growth, MMP activity, and invasion and induced apoptosis in vitro-important parameters for cancer development, suggesting NM as a potential treatment strategy for liposarcoma.
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PMID:Inhibition of cell invasion and MMP production by a nutrient mixture in malignant liposarcoma cell line SW-872. 1791 88

The study was aimed to reveal the effects of matrix metalloproteinase-2 (MMP-2) on cell proliferation, migration, invasion, angiogenesis and cell cycle. The small interfering RNA (siRNA) of MMP-2 transfected into endothelial cells EAhy926, the transformation efficiency at protein and gene levels was evaluated by using flow cytometry and RT-PCR respectively. MTT method was used to detect the proliferation ability of EAhy926. The migration and invasion abilities of EAhy926 induced by two kinds of factors, type IV collagen (COL IV) and fibronectin (Fn) were assayed with Rose Bengal dying method. The changes of angiogenesis were determined by three-dimension culture. The changes of cell cycle and related gene expression were assayed by using flow cytometry and RT-PCR respectively. The results indicated that the proliferation ability of EAhy926 had no obvious difference between interference or not. The migration ability of EAhy926 induced by two kinds of factors, type IV collagen (COL IV) and fibronectin (Fn) was inhibited after interfered by siRNA for 48 hours, and was stronger inhibition to COL IV than Fn (Fn control: 0.581+/-0.012 vs 0.261+/-0.002; COL IV control: 0.467+/-0.009 vs 0.110+/-0.010, p<0.01). The invasion test had the similar result as migration test. (Fn vs control: 0.365+/-0.012 vs 0.101+/-0.002; COL IV vs control: 0.317+/-0.009 vs 0.102+/-0.010, p<0.01). The angiogenesis ability of endothelial cells dropped to 58.9% of control after interference with siRNA for 48 hours. In the cell cycle experiments, after RNAi for 48 hours and 72 hours, the cell ratio of G1 rose from [(65.9+/-2.53)%; (63.2+/-1.89)%] to [(83.9+/-2.53)%, (89.2+/-1.24)%]% (p<0.01); the cell ratio of S and G2 dropped from [(32.7+/-1.91)%, (37.1+/-2.65)%] to [(18.1+/-1.49)%, (10.2+/-0.85)%] (p<0.01). The results analyzed by semi-quantitative RT-PCR showed that the expression levels of Rb, cyclin D1 PCNA genes dropped to 35%, 51% and 22% of normal control respectively. It is concluded that the expression of MMP-2 does not distinctly correlate with the proliferation of endothelial cells, but plays a very important role in affecting endothelial cell migration, invasion and angiogenesis, and participates in regulating cell cycle through Rb, cyclinD1 and PCNA.
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PMID:[Function of matrix metalloprotenase-2 by RNA interference]. 1842 70

Colorectal carcinoma (CRC) is often lethal when invasion and/or metastasis occur. NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme involved in prostaglandin (including PGE(2)) bio-inactivation, is down-expressed in several epithelial malignancies including CRC. Although its role in the suppression of colon tumorigenesis has been well learned, little is known about the role of 15-PGDH in the process of tumor metastasis. Here, we tested the hypothesis that 15-PGDH over-expression in CRC cells results in decreased cell motility and invasion. In this study, 15-PGDH was re-expressed in SW480 cells by the use of gene transient transfection with eukaryotic expression vector pcDNA3.1-PGDH. We confirmed the over-expression of 15-PGDH protein by Western blot and enzymatic activity assay. The cell motility was tested by counting the number of cells crossing an 8-micron pore size PET membrane and by measuring cells migration distance through wound healing assay. Furthermore, cell invasive activity was evaluated by counting the number of cells invading through a Matrigel-coated membrane simulating basement membrane. The effects of 15-PGDH on the adhesion were investigated by MTT assay. Ectopic expression of 15-PGDH in SW480 cancer cells significantly inhibited the cell migratory and invasive capacity in vitro by approximately 1.9- and 8.4-fold, respectively. To test the hypothesis that 15-PGDH affects proteases and inactivates extracellular matrix (ECM), Western blot and gelatin zymography were performed by using serum-free conditioned medium. The results showed that re-expression of 15-PGDH suppresed matrix metalloproteinase-2 (MMP2) synthesis and secretion. In addition, the analysis of the MMP2 activity indicated that re-expression of 15-PGDH could inhibit activation of MMP2. Furthermore, we found that 15-PGDH inhibited cell adhesion to ECM and reduced CD44 expression in SW480 cell. Taken together, these results suggest that induced 15-PGDH expression may contribute to the inhibition of the invasive and metastatic capacity of colon cancer cells in vitro.
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PMID:Suppression of invasive properties of colorectal carcinoma SW480 cells by 15-hydroxyprostaglandin dehydrogenase gene. 1903 72

Des-gamma-carboxy prothrombin (DCP) is an aberrant prothrombin produced by hepatocellular carcinoma (HCC) cells. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. However, the role of DCP in the development of angiogenesis is not well understood. Herein, we report the effects of DCP on growth and migration of human vascular endothelial cells. DCP significantly stimulated the proliferation of HUVEC (ECV304) cells in a dose and time dependent manner, as measured by the MTT assay. A continuous rapid migration of ECV304 cells was observed in the presence of DCP measured by the scratch wound assay. The continuous rapid invasive activity, measured by transwell chamber assay also showed that DCP increased endothelial cells migration through the reconstituted extracellular matrix (Matrigel). Further, the tube formation of vascular endothelial cells on 3-D Matrigel showed an increased number of branch points of ECV304 cells induced by DCP in a dose dependent manner. The levels of vascular endothelial cell growth-related angiogenic factors and matrix metalloproteinase were also examined. DCP significantly stimulated the expression levels of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 (latent and active). Together, these data suggest that DCP is a novel type of vascular endothelial growth factor that possesses potent mitogenic and migrative activities in angiogenesis of HCC.
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PMID:Des-gamma-carboxy prothrombin stimulates human vascular endothelial cell growth and migration. 1926 29

Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of cancer-related death of men in the United States. Epidermal growth factor (EGF) generated from bone tissue contributes to prostate cancer metastasis through stimulating matrix metalloproteinase (MMP) secretions from prostate cancer cells. In this study, in vitro invasion assay was performed by incubating penta-O-galloyl-beta-D-glucose (5GG) at various concentrations with 2 x 10(4) PC-3 cells for 48 h. The anti-invasive and cytotoxic effects of 5GG were found and evaluated on the human androgen-independent prostate cancer PC-3 cell line by MTT assays and Western blot analyses. 5GG inhibited the EGF-induced cell invasiveness and MMP-9 expression in a dose- and time-dependent manner by reducing the MMP-9 transcriptional activity. To explore the mechanisms for the 5GG-mediated regulation of MMP-9, we further examined the effects of 5GG on transcription factors, including NF-kappaB, AP-1, and mitogen-activated protein kinase (MAPK) activities. The results showed that 5GG suppressed the EGF-induced NF-kappaB nuclear translocation and also abrogated the EGF-induced activation of c-jun N-terminal kinase (JNK), an upstream modulator of NF-kappaB. Moreover, we showed that 5GG reduced EGFR expression through the proteasome pathway. These results suggest that 5GG may exert at least part of its anti-invasive effect in androgen-independent prostate cancer by controlling MMP-9 expression through the suppression of the EGFR/JNK pathway. Finally, 5GG suppresses invasion and tumorigenesis in nude mice treatment with intratibia injection of PC-3 cells. These in vitro and in vivo results suggest that 5GG may be a therapeutic candidate for the treatment of advanced prostate cancer.
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PMID:Penta-O-galloyl-beta-D-glucose suppresses prostate cancer bone metastasis by transcriptionally repressing EGF-induced MMP-9 expression. 1932 Apr 36

Head and neck squamous cell carcinomas (HNSCCs) are known for their aggressive growth and propensity to metastasize. The authors investigated the effect of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract on human HNSCC cell line FaDu in vivo and in vitro. Athymic male nude mice (n = 12) were inoculated with 3 x 10(6) FaDu cells subcutaneously and randomly divided into 2 groups: group A was fed a regular diet and group B a regular diet supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and their tumors were excised, weighted, and processed for histology. In vitro, FaDu cells were cultured in Dulbecco's modified Eagle's medium and exposed to NM at 0 to 1000 microg/mL in triplicate. Cell proliferation was assessed by MTT assay, matrix metalloproteinase (MMP) secretion by gelatinase zymography, invasion through Matrigel, apoptosis by live-green caspases, and cell morphology by hematoxylin-eosin staining. NM inhibited the growth of tumors by 55% (P = .0002) and exhibited dose-dependent toxicity on FaDu cells in vitro, with 53% (P = .0003) at 1000 microg/mL NM. Zymography revealed MMP-2 and phorbol 12-myristate 13-acetate-induced MMP-9 secretion. NM inhibited secretion of both MMPs in a dose-dependent manner, with virtual total inhibition at 1000 microg/mL. NM significantly inhibited FaDu invasion through Matrigel with total block at 1000 microg/mL. NM induced dose-dependent apoptosis. In conclusion, NM has therapeutic potential in the treatment of HNSCC by significantly suppressing tumor growth and significantly inhibiting MMP secretion and invasion of HNSCC cells in vitro.
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PMID:Marked inhibition of growth and invasive parameters of head and neck squamous carcinoma FaDu by a nutrient mixture. 1967 26

Nonsteroidal antiinflammatory drugs are widely used to treat sports-related tendon injuries or tendinopathy. This study was designed to investigate the effect of ibuprofen on expressions of types I and III collagen, as well as collagen-degrading enzymes including matrix metalloproteinase (MMP)-1, -2, -8, -9, and -13. Rat Achilles tendon cells were treated with ibuprofen and then underwent MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Reverse transcription-polymerase chain reaction was used to evaluate mRNA expressions of types I and III collagen, MMP-1, -2, -8, -9, and -13. Protein expressions of types I and III collagen, MMP-1, -8, and -13 were determined by Western blot analysis. Gelatin zymography was used to evaluate the enzymatic activities of MMP-2 and MMP-9. The results revealed that ibuprofen upregulated expressions of MMP-1, -8, -9, and -13, both at mRNA and protein levels. There was no effect of ibuprofen on mRNA and protein expressions of types I and III collagen. Gelatin zymography revealed that the enzymatic activity of MMP-9 was upregulated after ibuprofen treatment. In conclusion, ibuprofen upregulates the expressions of collagenases including MMP-1, -8, -9, and -13 without affecting the expressions of types I and III collagen. These findings suggest a molecular mechanism potentially accounting for the inhibition of tendon healing by ibuprofen.
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PMID:Ibuprofen upregulates expressions of matrix metalloproteinase-1, -8, -9, and -13 without affecting expressions of types I and III collagen in tendon cells. 1984 88

The influence of short hairpin RNA (shRNA)-mediated osteopontin (OPN) gene silencing on the proliferation and invasion of human renal cancer ACHN cells was investigated. Four types of OPN shRNA recombinant plasmids were constructed and RT-PCR assays were used to screen the most highly functional shRNA recombinant plasmids, which were transferred into the cultured ACHN cells by Lipofectamine 2000. The cells transfected by shRNA expression vectors (ACHN/OPN) were visualized under an inverted microscope and screened by G418. Untreated cells (ACHN) and cells transfected by mock vectors (ACHN/Vect) were used as control groups. The expression levels of OPN mRNA and protein were detected by real-time PCR and Western blot respectively. The cell cycle and ratios of apoptotic cells were assessed by flow cytometry. MTT method was used for drawing the growth curve and observing cell proliferation in vitro. The abilities of migration and invasion in three groups were measured by Transwell chamber test. The expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 in three groups were examined by Western blot. Our results showed that the recombinant plasmid could be successfully transferred into ACHN cells by Lipofectamine 2000. Compared with untreated cells, the expression levels of OPN mRNA and protein in ACHN/OPN cells were decreased by 59.68% and 76.42%, respectively (P<0.05), ACHN/OPN cells were blocked in S phase and apoptotic ratio increased significantly (P<0.05), however, no significant differences were found between ACHN/Vect and ACHN. Recombinant plasmid significantly attenuated expression levels of MMP-2 and MMP-9 proteins and suppressed the proliferation, migration, and invasion of ACHN cells. This study suggested that OPN may play an important role in the growth and invasion of human renal cancer ACHN cells, and these processes are correlated with the activations of MMP-2 and MMP-9. Our data provided preliminary experimental evidence for the feasibility of RNA interference technology in gene therapy of human renal cancer.
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PMID:Influence of osteopontin short hairpin RNA on the proliferation and invasion of human renal cancer cells. 2015 57

The traditional Chinese medicine, Hong-Qu, also called red mold rice in the United States and Europe, is used for treating blood stasis, a disorder related to hyperlipidemia and atherosclerosis. In addition to improving metabolic syndrome, extracts from Monascus-fermented rice inhibit the proliferation of various cancer cells in vitro and in vivo. The objective was to examine the effect of red mold rice ethanol extract (RMRE) on angiogenesis, invasion, and metastasis during tumor progression. RMRE significantly inhibited the proliferation of SW480 and SW620 human colorectal carcinoma cells in a dose- and time-dependent manner by using the MTT assay. A capillary-like network morphology was observed after the addition of 20 ng/mL vascular endothelial growth factor or SW620 culture-conditional medium, which was not seen after RMRE treatment. Moreover, spontaneous intravasation into Matrigel grafts of SW620 cells from the upper to the lower layers in the chick embryo chorioallantoic membrane (CAM) model was detected by the polymerase chain reaction (PCR) amplification of human Alu genomic DNA from the lower CAMs in the RMRE-untreated group. Neovascularization increased to 75.3% +/- 11.6% by SW620 cells onplant with Matrigel grafts in the CAM model. However, RMRE significantly reduced CAM neovascularization in a dose-dependent manner. Finally, RMRE effectively decreased the activity of matrix metalloproteinase (MMP)-7 as determined by reverse transcription PCR (RT-PCR), Western blotting, and casein zymography assays. In summary, Monascus-fermented products exert a potent effect on tumor growth and activation, suggesting that they may serve as supplementary agents in adjuvant cancer therapy.
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PMID:Effects of Monascus-fermented rice extract on malignant cell-associated neovascularization and intravasation determined using the chicken embryo chorioallantoic membrane model. 2035 49

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