Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor (TGF)-beta1 is a multifunctional polypeptide that regulates a variety of cellular processes. Several studies have indicated that it is associated with epithelial-mesenchymal transition, angiogenesis, migration and metastases in many types of malignant tumors. We have used a wound-healing assay and a Matrigel invasion assay to evaluate the effects of TGF-beta1 and TGF-beta receptor I kinase inhibitor (TRI) on the cell motility and invasiveness of the human oral squamous cell carcinoma (OSCC) cell lines SAS-L1 and HSC-3. While TGF-beta1 enhanced the migration and invasion of OSCC cells, TRI significantly suppressed the migration and invasion of these cells. Exogenous TGF-beta1 up-regulated the activity of type IV collagenase (gelatinase A and gelatinase B), whereas TRI down-regulated the activity of these matrix metalloproteinases. Western blot analysis revealed that TGF-beta1 enhanced the expression of alpha5, alphav, beta1, beta6 and alphavbeta3 integrin subunits, and these enhanced integrins were down-regulated by treatment with TRI. These results suggest that the inhibition of TGF-beta1 suppresses motility and invasiveness of OSCC cells via modulation of integrins and matrix-metalloproteinases. Therefore, targeting the TGF-beta1 signaling pathway could be beneficial in the treatment of patients with OSCC.
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PMID:Inhibition of TGF-beta1 suppresses motility and invasiveness of oral squamous cell carcinoma cell lines via modulation of integrins and down-regulation of matrix-metalloproteinases. 1908 63

Oral cancer is the fourth most common cause of death from cancer in Taiwanese men. Indirubin-3'-monoxime (I3M), a potent cyclin-dependent kinase inhibitor, has therapeutic effects in other cancer cells. In this study, we carried out in vitro assays to test cell viability, cell cycle progression, apoptosis, cell migration and invasion in this cancer type. In addition, using an oral tumorigenic animal model, we examined target gene and protein expression using real time qPCR, immunoblotting and immunohistochemical staining. Our results demonstrate that I3M has an anti-proliferative effect in both Cal-27 and HSC-3 oral cancer cell lines and that treatment of Cal-27 and HSC-3 cells with I3M results in apoptosis through the activation of cytochrome c. In addition, I3M interrupts the cell cycle in Cal-27 cells in a dose-dependent manner by arresting cells in the G2/M phase. We also found that I3M suppresses migration and invasion in Cal-27 cells by inhibiting the expression of focal adhesion kinase, urokinase-type plasminogen inhibitor, and matrix metalloproteinase 9. Moreover, we identified survivin as a target protein in I3M-treated oral cancer cells. Using an oral cancer mouse model, we demonstrate that topical application of an adhesive gel composed of I3M and poly(vinyl alcohol) (I3M/PVA) has dose-dependent anti-tumorigenic effects. Following treatment, the expression of survivin protein and mRNA was downregulated in cancerous tissues. Furthermore, plasma survivin levels were also reduced in the I3M-treated mice. These results suggest that topical application of I3M, a drug synthesized from indirubin, which is found in Qing-Dai - has therapeutic potential for treating oral cancer.
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PMID:An indirubin derivative, indirubin-3'-monoxime suppresses oral cancer tumorigenesis through the downregulation of survivin. 2396 71