title: The synergism between Belotecan and cisplatin in gastric cancer.
abstract: OBJECTIVE
  We wanted to demonstrate the anti-cancer effect and interaction between belotecan and cisplatin on gastric cancer cell line and we evaluated the mechanisms of this synergistic effect in vitro.
  
  
  METHODS
  The growth inhibitory effect of belotocan and cisplatin against several gastric cancer cell lines (SNU-5, SNU-16 and SNU-601) was estimated by tetrazolium dye assay. The effect of a combination treatment was evaluated by the isobologram method. The biochemical mechanisms for the interaction between the drugs were analyzed by measuring the formation of DNA interstrand cross-links (ICLs) and DNA topo-I activity.
  
  
  RESULTS
  Belotecan showed synergism with cisplatin for growth inhibitory effect on the gastric cancer cell lines SNU-5, and SNU-16, but this was subadditive on the SNU-601 cell line. The formation of DNA ICLs in SNU-16 cells by cisplatin was increased by combination with belotecan, but this was not affected in SNU-601 cells. The topo-I inhibition by belotecan was enhanced at high concentrations of cisplatin in SNU-16, but not in SNU-601 cells.
  
  
  CONCLUSIONS
  Belotecan and cisplatin show various combination effect against gastric cancer cells. The synergism between cisplatin and belotecan could be the result of one of the following mechanisms: the modulating effect of belotecan on the repair of cisplatin-induced DNA adducts and the enhancing effect of cisplatin on the belotecan-induced topo-I inhibitory effect.
authors.affiliation: Department of Internal Medicine, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Jung
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Song
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Kim
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Hyun-Soon
authors.initials: HS
authors.lastname: Jong
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.forename: Noe Kyoung
authors.initials: NK
authors.lastname: Kim