[Potentiation of cisplatin sensitivity of cisplatin-resistant human ovarian cancer cell lines by L-buthionine-S,R-sulfoximine].
We established two human ovarian cancer cell lines (KK and MH) from the ascites of patients who did not respond to cisplatin (CDDP)-based combination chemotherapy. These cell lines showed higher resistance to CDDP in vitro than HRA cells which were established previously in our laboratory, and also have cross resistance with its analogues. The amount of intracellular glutathione (GSH) in these cells correlated with the degree of resistance to CDDP and was high, but the intracellular platinum (Pt) uptake was unchanged. Preincubation with L-buthionine-S,R-sulfoximine (BSO) reduced cellular GSH in these cells to 9-25%, while the Pt uptake remained unchanged. When the CDDP-resistant KK and MH cells were incubated in the presence of 10 microM BSO, they were sensitized to CDDP and its analogues showing a decrease to 79-38% in the IC50 values. On the basis of these results, we conclude that GSH may be involved in the mechanisms of resistance to CDDP and its analogues in the KK and MH cells.
Department of Obstetrics and Gynecology, National Defence Medical College, Saitama.
K
K
Kudoh
T
T
Kita
J
J
Hirata
K
K
Ishii
H
H
Hiramatsu
Y
Y
Kikuchi
I
I
Nagata
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D019328:Buthionine Sulfoximine; D002945:Cisplatin / Q000494:pharmacology*; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D005978:Glutathione / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D002945:Cisplatin