TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000244741
  • Gene Name:CDKN1A (P21)
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:COX2 signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB14060
  • Drug Name:NS-398
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:hepatocellular carcinoma
  • Tissue:cell lines (HT-29,SW-1116)

Other information

  • Title:cell lines (HT-29,SW-1116)
  • Journal:Dig Liver Dis
  • Published:2003
  • PubMed ID:14567460
  • Abstract:Background:Cyclooxygenase (COX)-2 is up-regulated in most colorectal cancers. Chronic use of non-steroidal anti-inflammatory drugs, which target cyclooxygenases, have been shown to reduce the risk of these cancers. However, the mechanisms underlying this protective effect remain unclear. Aims:The aim of our study was to characterize the effects of two COX-2 selective inhibitors, NS-398 and nimesulide, on colorectal cancer cell proliferation, and to describe the molecular mechanisms involved. Materials and methods:HT-29 and SW-1116 cell lines were cultured with either NS-398 or nimesulide. Cell proliferation was assessed by staining DNA with crystal violet. Cell cycle repartition and apoptosis were analysed by flow cytometry. The expression of COX-1 and COX-2. and of two cyclin dependent kinase inhibitors, p21Cip1 and p27Kip1, was analysed by Western blotting and RT-PCR. Results:Both drugs dose-dependently inhibited cell proliferation and induced G1 cell cycle blockade. HT-29 cells were more sensitive to both drugs than SW-1116 cells. p21Cip1 and p27Kip1 were induced on both cell lines. Concomitant induction of p21Cip1 mRNA indicates transcriptional modulation, whereas induction of p27Kip1 only at the protein level suggests post-translational modulation. Conclusion:NS-398 and nimesulide inhibit colorectal cell proliferation through induction of p21Cip1 and p27Kip1.
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