title: Parthenolide, an NF-κB inhibitor, suppresses tumor growth and enhances response to chemotherapy in gastric cancer.
abstract: OBJECTIVE
  This study evaluated the sesquiterpene lactone parthenolide, an inhibitor of transcription factor nuclear factor-kappaB (NF-κB), in the treatment of gastric cancer in vitro and in vivo.
  
  
  METHODS
  In vitro, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to evaluate the effect of parthenolide on growth inhibition and chemosensitization to antitumor drugs of three gastric cancer cell lines (MKN-28, MKN-45 and MKN-74). Microarray analysis was performed to identify genes which were up- or down-regulated on the treatment of parthenolide. The isobologram analysis was introduced to evaluate the synergic effect of parthenolide on antitumor drugs. In vivo, the effect of parthenolide was investigated in a mouse peritoneal dissemination model with and without chemotherapy.
  
  
  RESULTS
  Parthenolide significantly inhibited cell growth in three gastric cancer cell lines. The phosphorylation of NF-κB was down-regulated by the treatment of parthenolide. The synergic effect of parthenolide was confirmed in combination with paclitaxel and cisplatin. In the peritoneal dissemination model, parthenolide significantly suppressed the disseminated nodules as a single agent and also enhanced chemosensitivity to paclitaxel. Furthermore, the combined therapy of parthenolide and paclitaxel significantly contributed to prolonging the survival duration.
  
  
  CONCLUSIONS
  The NF-κB inhibitor, parthenolide, may enhance chemosensitivity to paclitaxel in the treatment of patients with gastric cancer.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Itsuro
authors.initials: I
authors.lastname: Sohma
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Yurika
authors.initials: Y
authors.lastname: Sugita
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoshioka
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Shirakawa
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Moon
authors.forename: Shuji
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D015536:Down-Regulation; D005562:Formazans / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics; D013778:Tetrazolium Salts / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005562:Formazans; D016328:NF-kappa B; D012717:Sesquiterpenes; D013778:Tetrazolium Salts; C079782:MTT formazan; C002669:parthenolide; D017239:Paclitaxel; D002945:Cisplatin