The Significance of MMP-9 Over MMP-2 in HCC Invasiveness and Recurrence of Hepatocellular Carcinoma After Curative Resection

Chen, Rongxin; Cui, Jiefeng; Xu, Changde; Xue, Tong-Chun; Guo, Kun; Gao, Dongmei; Liu, Yinkun; Ye, Sheng‐Long; Ren, Zhigang

doi:10.1245/s10434-011-1836-7

Cited by 91 publications

(74 citation statements)

References 35 publications

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“…The majority of clinical data had revealed correlations between the expression of MMPs and advanced tumor stages, invasion, metastasis and decreased survival rates (46). Previous studies have demonstrated that several MMPs are overexpressed in HCC and that high expression levels of MMPs are associated with cancer progression and metastasis (47)(48)(49). It was therefore suggested that inhibitors of MMP activity may be investigated for the prevention or reduction of tumor metastasis.…”

Section: Mmp-9 Is a Direct Target Gene Of Mir-133a In Hccmentioning

confidence: 99%

“…In addition, these studies revealed an association between the overexpression of MMP-2 or -9 and the invasion and metastasis of HCC. Increased levels of MMP-9 in HCC also correlate with increased tumour recurrence and metastasis following resection (48,49,52). Hayasaka et al (53) reported that MMP-9 plasma levels were upregulated in HCC patients, particularly in patients who presented with macroscopic portal vein invasion, which suggested that MMP-9 may serve as a marker for transformation and invasion in HCC or as a therapeutic target for the inhibition of metastasis in HCC.…”

Section: Mmp-9 Is a Direct Target Gene Of Mir-133a In Hccmentioning

confidence: 99%

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MicroRNA-133a inhibits cell proliferation, colony formation ability, migration and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma

Chen

Zhao

et al. 2015

Molecular Medicine Reports

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Abstract. is downregulated in various types of human malignancy, including hepatocellular carcinoma (HCC), renal cell carcinoma, esophageal squamous cell carcinoma, bladder cancer, ileal carcinoid and rhabdomyosarcoma. The aim of the present study was to examine the effects of miR-133a on HCC cell proliferation, colony formation, migration and invasion. miR-133a was transfected into the HCC HepG2 and SMMC-7721 cell lines and the expression levels of miR-133a were determined; in addition, cell viability assays, colony formation assays, cell migration assays, cell invasion assays, western blot analyses and luciferase assays were performed in the HCC cell lines. The results demonstrated that miR-133a significantly inhibited cell proliferation, colony formation, migration and invasion in HepG2 and SMMC-7721 cells. To the best of our knowledge, the present study also provided the first evidence that miR-133a directly downregulated the expression of matrix metallopeptidase 9 (MMP-9) in the HCC cells. In conclusion, the results of the present study indicated that miR-133a may have suppressed cell proliferation, colony formation, migration and invasion via the downregulation of MMP-9 in HCC cell lines. Therefore, MMP-9 may be used for the development of novel molecular markers and therapeutic approaches to inhibit hepatocellular carcinoma metastasis.

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Section: Mmp-9 Is a Direct Target Gene Of Mir-133a In Hccmentioning

confidence: 99%

Section: Mmp-9 Is a Direct Target Gene Of Mir-133a In Hccmentioning

confidence: 99%

MicroRNA-133a inhibits cell proliferation, colony formation ability, migration and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma

Chen

Zhao

et al. 2015

Molecular Medicine Reports

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“…Matrix metalloproteinases-2 (MMP-2) and MMP-9, which represent 72 kD and 92 kD type IV collagenases, respectively, degrade the basement membrane of normal cells and result in tumor invasion and subsequent metastasis. The detection of high expression levels of MMP-2 and MMP-9 in HCC has been suggested as a biomarker for poor prognosis (8,9).…”

Section: Introductionmentioning

confidence: 99%

Regorafenib diminishes the expression and secretion of angiogenesis and metastasis associated proteins and inhibits cell invasion via NF-κB inactivation in SK-Hep1 cells

Liu

Wang³

2017

Oncology Letters

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Abstract. The aim of the present study was to investigate the effects of regorafenib on the nuclear factor κ-light-chain-enhancer of activated B cells (NF)-κB-modulated expression of angiogenesis-and metastasis-associated proteins and cell invasion in human hepatocellular carcinoma SK-Hep1 cells. The SK-Hep1 cells were treated with different concentrations of NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl) ethyl] quinazoline-4,6-diamine (QNZ) or regorafenib for 24 or 48 h. The effects of QNZ and regorafenib on cell viability, NF-κB activation, expression and secretion levels of angiogenesis-and metastasis-associated proteins and cell invasion were evaluated with MTT assays, western blotting, ELISA, gelatin zymography and cell invasion assays. The results demonstrated that QNZ and regorafenib significantly reduced the expression and secretion levels of the angiogenesis-and metastasis-associated proteins vascular endothelial growth factor, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)-2 and MMP-9, NF-κB activation and cell invasion. In conclusion, the inhibition of NF-κB activation induces anti-angiogenic and antimetastatic effects in SK-Hep1 cells. Regorafenib reduces the level of expression and secretion of angiogenesis-and metastasis-associated proteins and cell invasion through the suppression of NF-κB activation in SK-Hep1 cells.

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“…MMP-2 and MMP-9 are two members of the MMP family and they are the primary enzymes that degrade diffusely basal membrane type IV collagen (21). Early studies have demonstrated that MMP-2 and MMP-9 exhibited increased expression in patients with HCC, which may be a prediction of tumor recurrence and survival in patients with HCC following surgical resection (22,23). In the current study, the effects of emodin on MMP-2 and MMP-9 expression in cells were investigated and the results suggest that emodin significantly downregulated MAPKs are serine-threonine protein kinases that mediate a wide variety of cellular behaviors, including proliferation, differentiation, apoptosis, migration and invasion (24).…”

Section: Discussionmentioning

confidence: 99%

Emodin inhibits migration and invasion of MHCC-97H human hepatocellular carcinoma cells

Lin

Zhong

Liang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Emodin, an anthraquinone derivative from the root and rhizome of Rheum palmatum L., was found to have antitumor effects in different types of cancer by regulating multi-molecular targets. The aim of the present study was to explore the effect of emodin on the migration and invasion of MHCC-97H human hepatocellular carcinoma cells and the underlying molecular mechanisms. Firstly, it was demonstrated that emodin can inhibit cell proliferation and induce apoptosis of cells in a time-and dose-dependent manner, using a MTT assay and flow cytometry, respectively. However, when emodin concentration was <50 µmol/l, it had little effect on the inhibition of proliferation or the induction of apoptosis. Then, it was observed that emodin can significantly suppress cell migration and invasion with a treatment dose <50 µmol/l compared with the control (P<0.05), which was not attributed to a decrease in cell number. Further study demonstrated that emodin significantly suppressed the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 compared with the control, which may be mediated by the activation of the p38 mitogen-activated protein kinases (MAPK) signaling pathway and suppression of extracellular signal regulated kinase (ERK)/MAPK and phosphatidylinositol 3-kinase/Akt signaling pathways. Therefore, the present study, for the first time, used MHCC-97H cells, which have the high potential of malignant invasion, to demonstrate that emodin may inhibit cell migration and invasion. IntroductionHepatocellular carcinoma (HCC) is one of the most frequent malignancies worldwide, representing the fifth most common cause of cancer in men and the seventh in women, and the third most frequent cause of cancer-related mortality (1-3). Globally, there are ~750,000 new cases of liver cancer reported per year (4). Although surgical resection provides better results in patients with HCC in early stages, the long-term prognosis remains unsatisfactory because many patients are diagnosed at the advanced stage, and tumors have an inherent capacity for invasiveness and metastasis (5,6). At present, chemotherapy is commonly used in the treatment of metastatic HCC. However, this treatment remains ineffective due to its toxicity to normal cells and the rapid development of resistance. Therefore, to further explore the biology of metastasis and develop novel therapeutics that specifically target metastasis and metastatic progression are required (7,8).Increasing attention has been paid to drugs among traditional Chinese medicines, since these materials typically share high safety profiles and can effectively prevent and control metastasis (9,10). Rheum palmatum L. is a plant that has been widely used in Chinese medicine as a laxative for thousands of years. Emodin is an anthraquinone derivative from its root and rhizome (11). It has been reported that emodin possesses a number of biological properties such as anti-inflammatory, antiviral and anti-proliferative effects (12). In the context of cancer, several studies have indicated...

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The Significance of MMP-9 Over MMP-2 in HCC Invasiveness and Recurrence of Hepatocellular Carcinoma After Curative Resection

Abstract: MMP-9 is superior to MMP-2 for the prediction of tumor recurrence and survival in HCC patients after surgical resection.

Cited by 91 publications

References 35 publications

MicroRNA-133a inhibits cell proliferation, colony formation ability, migration and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma

MicroRNA-133a inhibits cell proliferation, colony formation ability, migration and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma

Regorafenib diminishes the expression and secretion of angiogenesis and metastasis associated proteins and inhibits cell invasion via NF-κB inactivation in SK-Hep1 cells

Emodin inhibits migration and invasion of MHCC-97H human hepatocellular carcinoma cells

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