title: RC-3095, a gastrin-releasing peptide receptor antagonist, synergizes with gemcitabine to inhibit the growth of human pancreatic cancer CFPAC-1 in vitro and in vivo.
abstract: OBJECTIVE
  Pancreatic cancer remains a lethal disease. In this study, we investigated the efficacy of a combination of gastrin-releasing peptide receptor antagonist RC-3095 and gemcitabine on pancreatic cancer CFPAC-1.
  
  
  METHODS
  The antiproliferation effects of RC-3095, gemcitabine, or the combination on pancreatic cancer were monitored in vitro. Nude mice bearing xenografts of CFPAC-1 cell received injections of the vehicle (control), RC-3095 (20 μg, subcutaneously, daily), gemcitabine (15 mg/kg, intraperitoneally, every 3 days), or the combination of RC-3095 and gemcitabine for 4 weeks. The histological changes and protein expression were tested using immunohistochemistry and Western blotting.
  
  
  RESULTS
  Treatment with the combination in culture exhibited a powerful inhibition effect on CFPAC-1 cell proliferation. In xenograft mice model, RC-3095 or gemcitabine significantly reduced the volume and weight of tumors after 4 weeks of treatment, as compared with controls. The combination more potently inhibited the tumor growth than either agent used individually. Immunohistochemistry and Western blotting showed gastrin-releasing peptide receptor/bombesin receptor subtype-3 positive cells and protein expression in tumors decreased by treatment with RC-3095 or gemcitabine alone or greater in combination.
  
  
  CONCLUSIONS
  Our data suggested that the combination could be considered for the possible new approaches for treatment of pancreatic cancers.
authors: From the Department of General Surgery, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors: Shu-Kun
authors: SK
authors: Hong
authors: Shi-Yong
authors: SY
authors: Yang
authors: Shao-Hua
authors: SH
authors: Yin
authors: Kun-Xing
authors: KX
authors: Yang
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015153:Blotting, Western; D001839:Bombesin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D010446:Peptide Fragments; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3; D003841:Deoxycytidine; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D001839:Bombesin; D000093542:Gemcitabine