The synergism between Belotecan and cisplatin in gastric cancer.
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.
Jung
Joo Young
JY
Department of Internal Medicine, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
Song
Sang Hyun
SH
Kim
Tae-Young
TY
Park
Jung Hyun
JH
Jong
Hyun-Soon
HS
Im
Seock-Ah
SA
Kim
Tae-You
TY
Bang
Yung-Jue
YJ
Kim
Noe Kyoung
NK