title: Inhibition of ADAM-17 more effectively down-regulates the Notch pathway than that of γ-secretase in renal carcinoma.
abstract: BACKGROUND
  Our study is to research the effect of inhibited ADAM-17 expression through the Notch pathway in renal carcinoma.
  
  
  METHODS
  Immunohistochemistry and western blot were used to examine the expression of ADAM-17 protein in renal cancer tissues. Proliferation and cell invasion of 786-o cells, as well as OS-RC-2 cells, after treatment with two different inhibitors of the Notch pathway, were examined by CCK-8 assay and Transwell assay, respectively. 786-o cell apoptosis was measured using the FCM test.
  
  
  RESULTS
  ADAM-17 was highly expressed in RCC tissues. Compared with blocking γ-secretase, a known mechanism of impairing Notch, blockade of ADAM-17 more effectively down-regulated the expressions of Notch1 and HES-1 proteins. Similarly, we found that the ADAM-17 inhibitor, Marimastat, could more efficiently reduce renal cell proliferation and invasive capacity in comparison with the γ-secretase inhibitor DAPT when used at the same dose. Similar results were obtained when apoptosis of 786-o was measured.
  
  
  CONCLUSIONS
  Compared with γ-secretase, inhibition of ADAM-17 expression more effectively inhibits Notch pathway-mediated renal cancer cell proliferation and invasion. ADAM-17 may be a new target for future treatment of renal carcinoma.
authors: Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250001, China.
authors: Zhen
authors: Z
authors: Guo
authors: Xunbo
authors: X
authors: Jin
authors: Haiyan
authors: H
authors: Jia
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D051881:Receptor, Notch1 / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000072056:Transcription Factor HES-1
chemical_list: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases; D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D006877:Hydroxamic Acids; D051881:Receptor, Notch1; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human; C100342:marimastat; C000606462:ADAM17 protein, human
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