title: Escin augments the efficacy of gemcitabine through down-regulation of nuclear factor-κB and nuclear factor-κB-regulated gene products in pancreatic cancer both in vitro and in vivo.
abstract: OBJECTIVE
  Pancreatic cancer is an aggressive malignancy, which generally develops resistance to chemotherapy. Agents that are safe and can sensitize cancer to chemotherapy are urgently needed. Escin, a natural mixture of triterpene saponins isolated from Aesculus wilsonii Rehd, has been demonstrated to possess anti-cancer activity both in vitro and in vivo. The anti-cancer activity of escin could be, in part, due to the inactivation of nuclear factor-κB (NF-κB). In contrast, chemotherapy including gemcitabine could activate NF-κB and lead to chemoresistance. Here, for the first time, we investigated whether escin, via the inactivation of NF-κB, would potentiate the antitumor activity of gemcitabine in pancreatic cancer.
  
  
  METHODS
  Cell viability and proliferation, apoptosis, NF-κB activity and the expression of NF-κB-linked genes were all examined in vitro. The antitumor effect of escin with or without gemcitabine in pancreatic cancer was also assessed using BxPC-3 xenografts subcutaneously established in BALB/c nude mice.
  
  
  RESULTS
  Escin not only potentiated the proliferation-inhibiting and apoptosis-inducing effect of gemcitabine in both BxPC-3 and PANC-1 cell lines in vitro, but also dramatically enhanced its suppressive effect on tumor growth in nude mice. The mechanism is at least partially due to the inhibition of NF-κB activity and consequent inhibition of c-Myc, COX-2, Cyclin D1, Survivin, Bcl-2 and Bcl-xL, and the activation of caspase-3.
  
  
  CONCLUSIONS
  These data suggest that escin, via inactivation of NF-κB, could potentiate the efficacy of gemcitabine in combating pancreatic cancer, which could be a novel and potentially important therapeutic approach for the treatment for pancreatic cancer.
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Nangang, Harbin, People's Republic of China.
authors.forename: Yong-Wei
authors.initials: YW
authors.lastname: Wang
authors.forename: Shuang-Jia
authors.initials: SJ
authors.lastname: Wang
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Zhou
authors.forename: Shang-Ha
authors.initials: SH
authors.lastname: Pan
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D004928:Escin / Q000008:administration & dosage / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D016328:NF-kappa B; D003841:Deoxycytidine; D004928:Escin; D000093542:Gemcitabine