Overexpression of Twist and Matrix Metalloproteinase-9 with Metastasis and Prognosis in Gastric Cancer

Gao, Xinjie; Yang, Xueqin; Wang, Bi-Cheng; Liu, Shaoping; Wang, Xinghuan

doi:10.7314/apjcp.2013.14.9.5055

Cited by 29 publications

(27 citation statements)

References 43 publications

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“…Furthermore, p-cymene is found to inhibit the TPA-enhanced invasiveness of HT-1080 cells. Taken together with previous reports that the augmented expression of MMP-9 is implicated in the metastatic phenotype of many cancers in vivo and in vitro, 23,24) p-cymene is likely to be useful for the prevention of tumor invasion and metastasis.…”

Section: Discussionsupporting

confidence: 69%

Novel Antitumor Invasive Actions of <i>p</i>-Cymene by Decreasing MMP-9/TIMP-1 Expression Ratio in Human Fibrosarcoma HT-1080 Cells

Liu

Sato

2016

Biological & Pharmaceutical Bulletin

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p-Cymene (4-isopropyltoluene) has been reported to have beneficial actions such as anti-inflammatory and antinociceptive activities. To evaluate whether p-cymene exhibits antitumor invasive actions, we examined the effects of p-cymene on the production of matrix metalloproteinase 9 (MMP-9)/gelatinase B and tissue inhibitor of metalloproteinases-1 (TIMP-1) in human fibrosarcoma HT-1080 cells. p-Cymene was found to dose-dependently inhibit the 12-O-tetradecanoylphorbol 13-acetate (TPA)-augmented production and gene expression of MMP-9 in HT-1080 cells. In contrast, p-cymene enhanced the TPA-augmented production and gene expression of TIMP-1 in HT-1080 cells. However, there was no change in the constitutive level of MMP-9 and TIMP-1 mRNAs and TIMP-1 protein in p-cymene-treated cells. In addition, we found that the in-vitro TPA-augmented invasiveness of HT-1080 cells was inhibited by p-cymene in a dose-dependent manner. Furthermore, p-cymene was found to suppress the constitutive and/or TPA-augmented phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) in HT-1080 cells. Thus, these results provide novel evidence that p-cymene is an effective candidate for the prevention of tumor invasion and metastasis through mechanisms that include the inhibition of MMP-9 expression and the augmentation of TIMP-1 production along with the suppression of ERK1/2 and p38 MAPK signal pathways in tumor cells.Key words p-cymene; tumor invasion; matrix metalloproteinase 9; tissue inhibitor of metalloproteinases-1; extracellular signal-regulated kinase 1/2 (ERK1/2); p38 mitogen-activated protein kinase (p38 MAPK)The proteolytic degradation of extracellular matrix (ECM) components in basement membranes and stroma tissues is requisite for progressing the invasion and metastasis of malignant tumor cells. Matrix metalloproteinases (MMPs) play a crucial role in ECM degradation, and different sets of MMPs concertedly act in ECM breakdown. 1,2) Gelatinase A (72-kDa type IV collagenase)/MMP-2 and gelatinase B (92-kDa type IV collagenase)/MMP-9 have been reported to facilitate tumor cell invasion and epithelial-mesenchymal transition as a promoter and/or modulator in normal and tumor cells in vivo and in vitro.3) On the other hand, the enzymic activity of MMPs and proteolytic activation of the MMP precursor (proMMP) have been reported to be controlled by endogenous inhibitors such as tissue inhibitors of metalloproteinases (TIMPs).4) Since four TIMPs have been identified, designated as TIMP-1, TIMP-2, TIMP-3, and TIMP-4, they inhibit MMPs by forming a strong noncovalent complex with a 1 : 1 stoichiometry. 4) Regarding the inhibitory properties among the TIMPs, TIMPs can bind to different sets of MMPs: e.g., the preference inhibition of TIMP-1 against MMP-9, MMP-3, and MMP-1, and that of TIMP-2 against MMP-2 rather than MMP-9.4,5) Therefore, the inhibition of expression and/or enzymic activity of MMP is likely to be an effective target(s) for preventing tumor invasion and metastasis.

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Section: Discussionsupporting

confidence: 69%

Novel Antitumor Invasive Actions of <i>p</i>-Cymene by Decreasing MMP-9/TIMP-1 Expression Ratio in Human Fibrosarcoma HT-1080 Cells

Liu

Sato

2016

Biological & Pharmaceutical Bulletin

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“…It has been found that the MMP9 15 , COX2 16 , c-Myc 17 genes are upregulated, and the CDKN2A (formerly p16) 18 and TP53 19 genes are downregulated. Here, we focused on changes in appl1 expression in gc and the relationships of appl1 and associated clinicopathologic characteristics with clinical prognosis.…”

Section: Discussionmentioning

confidence: 99%

Expression of APPL1 Is Correlated with Clinicopathologic Characteristics and Poor prognosis in Patients with Gastric Cancer

Zhai¹,

Song²,

Zhu³

et al. 2016

Current Oncology

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“…Numerous researchers have devoted themselves to exploring the pathogenesis of cancer and attempting to seek effective therapies against various cancers including gastric carcinoma. Multi-factors including abnormal expression, aberrant methylation and single nucleotide polymorphisms (SNPs) of genes that associated with cell proliferation, cell differentiation and other key cell processes have been identified to be related to tumorigenesis, in addition, small regulators such as microRNA also have been shown to play an important role in cancers (Guo et al, 2012;Jing et al, 2012;Chen et al, 2013;Gao et al, 2013;Yao et al, 2013;Zhu et al, 2013). Based on these advances of mechanisms, treatments against cancer are no longer confined to traditional chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Phenolic Alkaloids of Menispermum Dauricum on Gastric Cancer in Vivo

Zhang

Wu²,

Du³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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The present study was conducted to investigate effects and mechanisms of action of phenolic alkaloids of Menispermum dauricum (PAMD) on gastric cancer in vivo. In vitro, cell apoptosis of human gastric cancer cell line SGC-7901 was observed using fluorescence staining. In vivo, a mice model was constructed to observe tumor growth with different doses. Cell apoptosis was examined using flow cytometry and K-RAS protein expression using Western blotting. The mRNA expression of P53, BCL-2, BAX, CASPASE-3, K-RAS was examined by real-time PCR. PAMD significantly suppressed tumor growth in the xenograft model of gastric cancer in a dosedependent manner (p<0.01). Functionally, PAMD promoted cell apoptosis of the SGC-7901 cells and significantly increased the rate of cell apoptosis of gastric tumor cells (p<0.05). Mechanically, PAMD inhibited the expression of oncogenic K-RAS both at the mRNA and protein levels. In addition, PAMD affected the mRNA expression of the cell apoptosis-related genes (P53, BCL-2, BAX, CASPASE-3). PAMD could suppress gastric tumor growth in vivo, possibly through inhibiting oncogenic K-RAS, and induce cell apoptosis possibly by targeting the cell apoptosis-related genes of P53, BCL-2, BAX, CASPASE-3.Keywords: Gastric cancer -cell apoptosis -in vivo -K-RAS -phenolic alkaloids of menispermumdauricum RESEARCH ARTICLE

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Overexpression of Twist and Matrix Metalloproteinase-9 with Metastasis and Prognosis in Gastric Cancer

Cited by 29 publications

References 43 publications

Novel Antitumor Invasive Actions of <i>p</i>-Cymene by Decreasing MMP-9/TIMP-1 Expression Ratio in Human Fibrosarcoma HT-1080 Cells

Novel Antitumor Invasive Actions of <i>p</i>-Cymene by Decreasing MMP-9/TIMP-1 Expression Ratio in Human Fibrosarcoma HT-1080 Cells

Expression of APPL1 Is Correlated with Clinicopathologic Characteristics and Poor prognosis in Patients with Gastric Cancer

Inhibitory Effects of Phenolic Alkaloids of Menispermum Dauricum on Gastric Cancer in Vivo

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