title: [Effects of 17-DMAG on non-small cell lung cancer cell lines A549 and H1975  being resistant to EGFR-TKI].
abstract: OBJECTIVE
  In the clinical treatment of patients with non-small cell lung cancer (NSCLC), the primary and acquired resistance of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) limits its clinical application, this need to explore new strategy or method to overcome this problem. Recently, some literatures have indicated that the antitumor role of heat shock protein 90 (HSP90) inhibitors by a variety of pathways may provide new strategy for resolving this problem. In this study, we examined the effect of 17-DMAG on NSCLC cell lines A549 and H1975 which were primary and acquired resistant to EGFR-TKI respectively, the purpose was to explore its influence on cell proliferation, apoptosis and the expression of EGFR in vitro as well as possible mechanism.
  
  
  METHODS
  After A549 and H1975 cell lines were treated with different concentrations of 17-DMAG respectively, the inhibitory rate of cell proliferation was measured by MTT assay in 24 h, 48 h and 72 h. We investigated the effect of 17-DMAG on the cell apoptosis with flow cytometry and the expression of HSP90 and EGFR with Western blot after treated with 17-DMAG for 48 h.
  
  
  RESULTS
  After treated with 17-DMAG, the inhibitory rate of different concentrations and time groups was significant (P<0.01), and the effect was in time- and dose-dependent manner; the apoptosis rate of both two cell lines in all treated groups were significantly higher than control group (P<0.01), and the effect was in dose-dependent manner. By Western blot analysis, there was no significant difference between all treated groups and control group for the expression of both HSP90 and EGFR protein in A549 cell line and HSP90 protein in H1975 cell line after exposed to 17-DMAG for 48 h (P>0.05), while the difference was significant for the expression of EGFR protein in H1975 cell line (P<0.01).
  
  
  CONCLUSIONS
  17-DMAG inhibited the proliferation of NSCLC cell lines A549 and H1975 and also induced apoptosis of both cell lines. It down-regulated the expression of mutant EGFR protein while this phenomenon was not observed in EGFR-wild type cell line. This suggested that the mechanism maybe different between A549 and H1975 cell lines with different genetic backgroud. Our study provided new strategy for treatment with NSCLC being resistant to EGFR-TKI.
authors.affiliation: Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Fumin
authors.initials: F
authors.lastname: Cao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D066246:ErbB Receptors / Q000378:metabolism; D005434:Flow Cytometry; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D047428:Protein Kinase Inhibitors; C448659:17-(dimethylaminoethylamino)-17-demethoxygeldanamycin; D066246:ErbB Receptors