title: ABT-737 synergizes with arsenic trioxide to induce apoptosis of gastric carcinoma cells in vitro and in vivo.
abstract: OBJECTIVE
  This study investigated the potential synergistic effects of two inducers of apoptosis: the small molecule ABT-737 and arsenic trioxide (ATO).
  
  
  METHODS
  Human gastric carcinoma cell lines SGC-7901 and MGC-803 were used to determine the effects of ABT-737 and ATO (alone or  in combination) on cell proliferation and apoptosis in vitro. In vivo effects of these drugs were investigated in SGC-7901 solid tumours, grown in immunodeficient mice.
  
  
  RESULTS
  ABT-737 and ATO inhibited proliferation and induced apoptosis in SGC-7901 and MGC-803 cells in concentration-  and time-dependent manners, and showed a synergistic effect. ABT-737 disturbed the binding of B cell lymphoma (Bcl)-2 homologous antagonist killer and Bcl-extra large; ATO downregulated myeloid cell leukaemia (Mcl)-1 protein and upregulated Mcl-1short, the short splicing variant. ABT-737 and  ATO significantly suppressed SGC-7901 xenograft growth, synergistically inhibited tumour growth and induced apoptosis in vivo.
  
  
  CONCLUSIONS
  This study provides preclinical evidence that ABT-737 and ATO synergize to induce apoptosis of gastric carcinoma cells, suggesting that further  investigation of these agents (as potential treatments for gastric cancer) is warranted.
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: X P
authors.initials: XP
authors.lastname: Sun
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: He
authors.forename: H
authors.initials: H
authors.lastname: Qiao
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: X
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D001713:Biphenyl Compounds / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009596:Nitrophenols / Q000008:administration & dosage; D010087:Oxides / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C501332:ABT-737; D051017:Apoptosis Regulatory Proteins; D001152:Arsenicals; D001713:Biphenyl Compounds; D009596:Nitrophenols; D010087:Oxides; D010879:Piperazines; D013449:Sulfonamides; D000077237:Arsenic Trioxide