[The mechanism of resistance and its circumvention of cisplatin-resistant human ovarian cancer cells].
In this study, we attempted to elucidate the mechanisms of cisplatin resistance and circumvent the resistance with calmodulin antagonists using a cisplatin-resistant human ovarian cancer cell line (KFr). It was assumed that the cisplatin resistance resulted from impairment of cisplatin transport systems. In particular, we considered that a reduced cisplatin transport function caused by some amino acids had an effect on the resistance mechanism. Reduced uptake of cisplatin as well as cisplatin analogues to KFr cells was observed. Four cisplatin analogues used in this study had cross-resistance to cisplatin. However, the concentration of drugs incorporated into cells was not always correlated with the degree of resistance. Therefore, it is possible that, in addition to the reduced influx function, an other mechanism is involved in the resistance. Combined treatment with cisplatin and calmodulin antagonists significantly increased the uptake of cisplatin by KFr cells and maintained the cellular level. Thus, a combination therapy of cisplatin and calmodulin antagonists seemed to be of clinical use.
Kikuchi
Y
Y
Department of Obstetrics and Gynecology, National Defense Medical College, Saitama.
Iwano
I
I
Miyauchi
M
M
Kita
T
T
Kuki
E
E
Nagata
I
I
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002945:Cisplatin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D004351:Drug Resistance / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D002147:Calmodulin; D013449:Sulfonamides; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D002945:Cisplatin