title: [SOCS1 knockdown sensitize anti-tumor activity of IFN-alpha2a-NGR].
abstract: OBJECTIVE
  Search for key molecules to influence the tumor-targeted IFN-alpha2a-NGR anti-tumor sensitivity through signaling pathway study. Try to enhance the antitumor efficacy of IFN-alpha2a-NGR.
  
  
  METHODS
  MTT method was used to determine the growth inhibitory effects of IFN-alpha2a-NGR on A549 and MKN-45 cells. Flow cytometry and Western blot were employed to detect the expression of STAT1, p-STAT1, p53, OAS and SOCS1; SOCS1 gene knock down was carried out by synthesized siRNA.
  
  
  RESULTS
  When stimulated with IFN-alpha2a-NGR, the increased expression of STAT1, p-STAT1, p53, OAS and SOCS1 were observed in A549 cells, but only SOCS1 was notably increased in MKN-45 cells. The proliferation inhibition ability of MKN-45 to IFN-alpha2a-NGR was promoted by SOCS1 knocking down. (the inhibition rate was enhanced from 14.69%+/-1.05% to 36.97%+/-2.05%).
  
  
  CONCLUSIONS
  This study has further demonstrated that there were no differences on antitumor effects between IFN-alpha2a-NGR and IFN-alpha2a on cell or molecular level. Besides interferon-alpha receptor (IFNAR) which has been demonstrated before, p-STAT1, p53 and SOCS1 were important determinants of tumor resistance to IFNs therapy. The antitumor efficacy of IFN-alpha2a-NGR can be enhanced by RNA interference. These results might be helpful for the further development of IFN-alpha2a-NGR.
authors.affiliation: State Key Laboratory of Tumor Biology; Department of Pharmacogenomics, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Qi-chao
authors.initials: QC
authors.lastname: Huang
authors.forename: Xiao-ying
authors.initials: XY
authors.lastname: Lei
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Wen-jun
authors.initials: WJ
authors.lastname: Sui
authors.forename: Shen
authors.initials: S
authors.lastname: Li
authors.forename: Ying-qi
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D010455:Peptides; D011993:Recombinant Fusion Proteins; C108944:SOCS1 protein, human; D050794:STAT1 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016159:Tumor Suppressor Protein p53