title: Synergistic antitumor effect of triptolide and cisplatin in cisplatin resistant human bladder cancer cells.
abstract: OBJECTIVE
  We examined the synergistic antitumor effects of cisplatin combined with triptolide in cisplatin resistant T24R2 bladder cancer cells and investigated possible molecular mechanisms.
  
  
  METHODS
  T24R2 cells were treated with cisplatin and/or triptolide. Tumor cell proliferation was determined using cell counting and clonogenic assays. The combination index of the synergism between cisplatin and triptolide was calculated. The cell cycle phase and apoptosis rate were determined by flow cytometry. Apoptosis and cell cycle related protein expression were analyzed by Western blot.
  
  
  RESULTS
  The synergistic cytotoxicity effect of cisplatin and triptolide combination treatment was greater than the cytotoxic effect of cisplatin or triptolide alone. Combination treatment also induced cell cycle arrest via cyclin D1 and E1 expression. Apoptosis induced by combination treatment was accompanied by increased expression of caspase-3, 8 and 9, PARP and cytochrome c.
  
  
  CONCLUSIONS
  Our results suggest that triptolide synergistically enhanced the antitumor effect of cisplatin in cisplatin resistant human bladder cancer cells. Cisplatin and triptolide combination treatment may be effective for advanced bladder cancer.
authors.affiliation: Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jin-Nyoung
authors.initials: JN
authors.lastname: Ho
authors.affiliation: Biomedical Research Institute and Department of Urology, School of Medicine, Seongnam, Republic of Korea. Electronic address: ssbyun@snubh.org.
authors.forename: Seok-Soo
authors.initials: SS
authors.lastname: Byun
authors.affiliation: Biomedical Research Institute and Department of Urology, School of Medicine, Seongnam, Republic of Korea.
authors.forename: Sangchul
authors.initials: S
authors.lastname: Lee
authors.affiliation: Biomedical Research Institute and Department of Urology, School of Medicine, Seongnam, Republic of Korea.
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Oh
authors.affiliation: Biomedical Research Institute and Department of Urology, School of Medicine, Seongnam, Republic of Korea.
authors.forename: Sung Kyu
authors.initials: SK
authors.lastname: Hong
authors.affiliation: Biomedical Research Institute and Department of Urology, School of Medicine, Seongnam, Republic of Korea.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Biomedical Research Institute and Department of Urology, School of Medicine, Seongnam, Republic of Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Yeon
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide; D002945:Cisplatin
keywords: cisplatin; combination; drug resistance; drug therapy; triptolide; urinary bladder neoplasms